1,555 results on '"Testis radiation effects"'
Search Results
2. Effects of low-dose rate radiation on immune and epigenetic regulation of the mouse testes.
- Author
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Uemura I, Takahashi-Suzuki N, Kuroda S, Kumagai K, Tsutsumi Y, Anderson D, Satoh T, Yamashiro H, Miura T, Yamauchi K, and Nakata A
- Subjects
- Animals, Male, Mice, Dose-Response Relationship, Radiation, Immunity, Innate radiation effects, Radiation Dosage, Testis radiation effects, Testis metabolism, Epigenesis, Genetic radiation effects
- Abstract
This study investigated the effects of chronic low-dose-rate radiation exposure on gene expression related to immunological defense mechanisms and epigenetic regulation in the testis of male mice. The study found that radiation exposure (4.5 mGy/hr until 4000 mGy) led to a significant decrease in the expression of genes involved in epigenetic regulation and a significant increase in the expression of several genes linked to innate and acquired immunity, suggesting a noticeable effect on the immune response. In addition, there was a significant increase in the expression of SRY-box transcription factor 9, which plays a crucial role in testicular development, indicating a response to irradiation. These findings provide insights into the biological effects of chronic low-dose-rate radiation exposure on innate immunity and epigenetic regulation in the testis., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2024
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3. Short and long-term 2100 MHz radiofrequency radiation causes endoplasmic reticulum stress in rat testis.
- Author
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Kirimlioglu E, Oflamaz AO, Hidisoglu E, Ozen S, Yargicoglu P, and Demir N
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- Animals, Male, Rats, Radio Waves adverse effects, Apoptosis radiation effects, Endoplasmic Reticulum Stress radiation effects, Testis radiation effects, Testis metabolism, Rats, Sprague-Dawley
- Abstract
Long-term radiofrequency radiation (RFR) exposure, which adversely affects organisms, deteriorates testicular functions. Misfolding or unfolding protein accumulation in the endoplasmic reticulum (ER) initiates an intracellular reaction known as ER stress (ERS), which activates the unfolded protein response (UPR) for proteostasis. Since both RFR exposure and ERS can cause male infertility, we hypothesized that RFR exposure causes ERS to adversely affect testicular functions in rats. To investigate role of ERS in mediating RFR effects on rat testis, we established five experimental groups in male rats: control, short-term 2100-megahertz (MHz) RFR (1-week), short-term sham (sham/1-week), long-term 2100-MHz RFR (10-week), and long-term sham (sham/10-week). ERS markers Grp78 and phosphorylated PERK (p-Perk) levels and ERS-related apoptosis markers Chop and caspase 12 were investigated by immunohistochemistry, immunoblotting, and quantitative real-time polymerase chain reaction (qPCR). Long-term RFR exposure increased Grp78, p-Perk, and Chop levels, while short-term RFR exposure elevated Chop and caspase 12 levels. Chop expression was not observed in spermatogonia and primary spermatocytes, which may protect spermatogonia and primary spermatocytes against RFR-induced ERS-mediated apoptosis, thereby allowing transmission of genetic material to next generations. While short and long-term RFR exposures trigger ERS and ERS-related apoptotic pathways, further functional analyses are needed to elucidate whether this RFR-induced apoptosis has long-term male infertility effects., (© 2024. The Author(s).)
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- 2024
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4. Prostate radiotherapy may cause fertility issues: a retrospective analysis of testicular dose following modern radiotherapy techniques.
- Author
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Kissel M, Terlizzi M, Giraud N, Alexis A, Cheve M, Vautier J, Bossi A, Morice P, and Blanchard P
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- Humans, Male, Retrospective Studies, Middle Aged, Organs at Risk radiation effects, Aged, Adult, Radiation Injuries etiology, Fertility radiation effects, Prostatic Neoplasms radiotherapy, Testis radiation effects, Radiotherapy Dosage, Radiotherapy, Intensity-Modulated adverse effects, Radiotherapy, Intensity-Modulated methods, Radiotherapy Planning, Computer-Assisted methods
- Abstract
Background: Prostate cancer in younger men is rare but not exceptional. Radiotherapy is a cornerstone of prostate cancer treatment and yet, its impact on fertility is scarcely reported in literature. Given the radiosensitivity of testicular tissue, this study aimed to determine the testicular dose using modern radiotherapy techniques for definitive prostate irradiation., Methods: One hundred radiotherapy plans were reviewed. Testicles were contoured retrospectively without dosimetric optimization on testicles., Results: The median testicular dose was 0.58 Gy: 0.18 Gy in stereotactic plans, 0.62 Gy in Volumetric Modulated Arc Therapy plans and 1.50 Gy in Tomotherapy plans (p < 0.001). Pelvic nodal irradiation increased the median testicular dose to 1.18 Gy versus 0.26 Gy without nodal irradiation (p < 0.001). Weight and BMI were inversely associated with testicular dose (p < 0.005). 65% of patients reached the theoretical dose threshold for transient azoospermia, and 10% received more than 2 Gy, likely causing definitive azoospermia., Conclusion: Despite being probably lower than doses from older techniques, the testicular dose delivered with modern prostate radiotherapy is not negligible and is often underestimated because the contribution of daily repositioning imaging is not taken into account and most Treatment Planning Systems underestimate the out of field dose. Radiation oncologists should consider the impact on fertility and gonadal endocrine function, counseling men on sperm preservation if they wish to maintain fertility., Trial Registration: retrospectively registered., (© 2024. The Author(s).)
- Published
- 2024
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5. Decreased spermatogonial numbers in boys with severe haematological diseases.
- Author
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Lahtinen AK, Funke M, Krallmann C, Wyrwoll MJ, Jarisch A, Yang Y, Bjarnason R, Romerius P, Sundin M, Norén-Nyström U, Langenskiöld C, Cremers JF, Kliesch S, Stukenborg JB, Neuhaus N, and Jahnukainen K
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- Humans, Male, Child, Child, Preschool, Adolescent, Fertility Preservation methods, Testis pathology, Testis radiation effects, Spermatogenesis radiation effects, Infant, Myelodysplastic Syndromes therapy, Spermatogonia pathology, Hematologic Diseases therapy, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
This study examines spermatogonial numbers in testicular samples from 43 prepubertal patients undergoing haematopoietic stem cell transplantation (HSCT). High-dose chemotherapy and/or radiation during HSCT can impact spermatogenesis requiring fertility preservation. Results show that 49% of patients have decreased and 19% severely depleted spermatogonial pool prior to HSCT. Patients with Fanconi anaemia exhibit significantly reduced spermatogonial numbers. Patients with immunodeficiency or aplastic anaemia generally present within the normal range, while results in patients with myelodysplastic syndrome or myeloproliferative neoplasm vary. The study emphasizes the importance of assessing spermatogonial numbers in patients with severe haematological diseases for informed fertility preservation decisions., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
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- 2024
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6. SCF/C-kit drives spermatogenesis disorder induced by abscopal effects of cranial irradiation in mice.
- Author
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Guo L, Qin T, Wang X, Zhang K, Liu L, Xue Y, Lai P, Li J, Li J, Wang F, Li W, and Ding G
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- Animals, Male, Mice, Testis radiation effects, Testis pathology, Signal Transduction radiation effects, Stem Cell Factor metabolism, Inflammation, Spermatogenesis radiation effects, Mice, Inbred C57BL, Proto-Oncogene Proteins c-kit metabolism, Oxidative Stress radiation effects, Cranial Irradiation adverse effects
- Abstract
Cranial radiotherapy is a major treatment for leukemia and brain tumors. Our previous study found abscopal effects of cranial irradiation could cause spermatogenesis disorder in mice. However, the exact mechanisms are not yet fully understood. In the study, adult male C57BL/6 mice were administrated with 20 Gy X-ray cranial irradiation (5 Gy per day for 4 days consecutively) and sacrificed at 1, 2 and 4 weeks. Tandem Mass Tag (TMT) quantitative proteomics of testis was combined with bioinformatics analysis to identify key molecules and signal pathways related to spermatogenesis at 4 weeks after cranial irradiation. GO analysis showed that spermatogenesis was closely related to oxidative stress and inflammation. Severe oxidative stress occurred in testis, serum and brain, while serious inflammation also occurred in testis and serum. Additionally, the sex hormones related to hypothalamic-pituitary-gonadal (HPG) axis were disrupted. PI3K/Akt pathway was activated in testis, which upstream molecule SCF/C-Kit was significantly elevated. Furthermore, the proliferation and differentiation ability of spermatogonial stem cells (SSCs) were altered. These findings suggest that cranial irradiation can cause spermatogenesis disorder through brain-blood-testicular cascade oxidative stress, inflammation and the secretory dysfunction of HPG axis, and SCF/C-kit drive this process through activating PI3K/Akt pathway., Competing Interests: Declaration of Competing Interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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7. Expression levels of tam receptors and ligands in the testes of rats exposed to short and middle-term 2100 MHz radiofrequency radiation.
- Author
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Katirci E, Kirimlioglu E, Oflamaz AO, Hidisoglu E, Cernomorcenco A, Yargıcoğlu P, Ozen S, and Demir N
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- Animals, Male, Rats, Apoptosis radiation effects, Axl Receptor Tyrosine Kinase, Caspase 3 metabolism, Intercellular Signaling Peptides and Proteins, Ligands, Rats, Wistar, Spermatogenesis radiation effects, Time Factors, Radio Waves adverse effects, Receptor Protein-Tyrosine Kinases metabolism, Testis metabolism, Testis radiation effects
- Abstract
With advances in technology, the emission of radiofrequency radiation (RFR) into the environment, particularly from mobile devices, has become a growing concern. Tyro 3, Axl, and Mer (TAM) receptors and their ligands are essential for spermatogenesis and testosterone production. RFR has been shown to induce testicular cell apoptosis by causing inflammation and disrupting homeostasis. This study aimed to investigate the role of TAM receptors and ligands in the maintenance of homeostasis and elimination of apoptotic cells in the testes (weeks), short-term sham exposure (sham/1 week), and middle-term sham exposure (sham/10 weeks). Testicular morphology was assessed using hematoxylin-eosin staining, while immunohistochemical staining was performed to assess expression levels of TAM receptors and ligands in the testes of all groups. The results showed that testicular morphology was normal in the control, sham/1 week, and sham/10 weeks groups. However, abnormal processes of spermatogenesis and seminiferous tubule morphology were observed in RFR exposure groups. Cleaved Caspase 3 immunoreactivity showed statistically significant difference in 1 and 10 weeks exposure groups compared to control group. Moreover, there was no significant difference in the immunoreactivity of Tyro 3, Axl, Mer, Gas 6, and Pros 1 between groups. Moreover, Tyro 3 expression in Sertoli cells was statistically significantly increased in RFR exposure groups compared to the control. Taken together, the results suggest that RFR exposure negatively affects TAM signalling, preventing the clearance of apoptotic cells, and this process may lead to infection and inflammation. As a result, rat testicular morphology and function may be impaired., (© 2024 Bioelectromagnetics Society.)
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- 2024
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8. Testicular Dysfunction in Male Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.
- Author
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Baliga S, Patel S, Naqa IE, Li XA, Cohen LE, Howell RM, Hoppe BS, Constine LS, Palmer JD, Hamstra D, and Olch AJ
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- Humans, Male, Child, Oligospermia etiology, Sperm Count, Young Adult, Adolescent, Infertility, Male etiology, Neoplasms radiotherapy, Radiotherapy Dosage, Radiation Injuries etiology, Adult, Organs at Risk radiation effects, Testis radiation effects, Cancer Survivors, Testosterone blood, Follicle Stimulating Hormone blood, Luteinizing Hormone blood
- Abstract
Purpose: The male reproductive task force of the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative performed a comprehensive review that included a meta-analysis of publications reporting radiation dose-volume effects for risk of impaired fertility and hormonal function after radiation therapy for pediatric malignancies., Methods and Materials: The PENTEC task force conducted a comprehensive literature search to identify published data evaluating the effect of testicular radiation dose on reproductive complications in male childhood cancer survivors. Thirty-one studies were analyzed, of which 4 had testicular dose data to generate descriptive scatter plots. Two cohorts were identified. Cohort 1 consisted of pediatric and young adult patients with cancer who received scatter radiation therapy to the testes. Cohort 2 consisted of pediatric and young adult patients with cancer who received direct testicular radiation therapy as part of their cancer therapy. Descriptive scatter plots were used to delineate the relationship between the effect of mean testicular dose on sperm count reduction, testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) levels., Results: Descriptive scatter plots demonstrated a 44% to 80% risk of oligospermia when the mean testicular dose was <1 Gy, but this was recovered by >12 months in 75% to 100% of patients. At doses >1 Gy, the rate of oligospermia increased to >90% at 12 months. Testosterone levels were generally not affected when the mean testicular dose was <0.2 Gy but were abnormal in up to 25% of patients receiving between 0.2 and 12 Gy. Doses between 12 and 19 Gy may be associated with abnormal testosterone in 40% of patients, whereas doses >20 Gy to the testes were associated with a steep increase in abnormal testosterone in at least 68% of patients. FSH levels were unaffected by a mean testicular dose <0.2 Gy, whereas at doses >0.5 Gy, the risk was between 40% and 100%. LH levels were affected at doses >0.5 Gy in 33% to 75% of patients between 10 and 24 months after radiation. Although dose modeling could not be performed in cohort 2, the risk of reproductive toxicities was escalated with doses >10 Gy., Conclusions: This PENTEC comprehensive review demonstrates important relationships between scatter or direct radiation dose on male reproductive endpoints including semen analysis and levels of FSH, LH, and testosterone., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2024
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9. Rosmarinic Acid Protects the Testes of Rats against Cell Phone and Ultra-high Frequency Waves Induced Toxicity.
- Author
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Fatahi Asl J, Goudarzi M, Mansouri E, and Shoghi H
- Subjects
- Animals, Male, Rats, Antioxidants pharmacology, Rosmarinic Acid, Depsides pharmacology, Cinnamates pharmacology, Testis drug effects, Testis radiation effects, Rats, Wistar, Cell Phone, Oxidative Stress drug effects
- Abstract
Background: Cell phone and Ultra-High Frequency (UHF) waves produce oxidative stress and cause testicular toxicity. This investigation was directed to evaluate the effectiveness of Rosmarinic Acid (RA) against oxidative stress caused by UHF radiation in rats., Methods: Forty-two male Wistar rats were divided into six groups. The control received 5 mL normal saline (0.9% NaCl) by gavage, the cell phone group received 915 MHz, the UHF waves group just received 2450 MHz, the RA/cell phone group received RA plus 915 MHz, RA/UHF waves group received RA plus 2450 MHz, and RA just received RA (20 mg/kg). After 30 days of consecutive radiation, the biochemical and histopathological parameters of their testes were measured. Statistical comparison was made using one-way ANOVA followed by Tukey's post hoc test., Results: Cell phone and UHF wave radiation significantly diminished the activity of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, and glutathione content (P<0.001). On the opposite, UHF significantly increased oxidative stress indices including malondialdehyde level, nitric oxide level, and protein carbonyl content (P<0.001). UHF also significantly reduced the number of Sertoli cells, spermatogonia, primary spermatocyte, epithelial height, and seminiferous tubular and luminal diameters (P<0.001). RA, as an effective antioxidant, reverses the above-mentioned harms and moderates the adverse effects of UHF on the testes of rats by significantly diminishing the oxidative stress indices and antioxidant enzyme rise and improving the histological parameters (P<0.001)., Conclusion: RA can protect the testes of rats from UHF-induced toxicity by reducing oxidative stress. RA as a food supplement might be useful for protecting humans exposed to UHF environmental contamination., Competing Interests: None declared., (Copyright: © Iranian Journal of Medical Sciences.)
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- 2024
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10. The histological and biochemical analysis of the effects of radiofrequency radiation on testis tissue of rats and the protective effect of melatonin.
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Yardim A, Sirav B, Tomruk A, Oruç S, Delen K, Kuzay D, Seymen CM, and Take Kaplanoğlu G
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- Male, Animals, Rats, Antioxidants pharmacology, Malondialdehyde metabolism, Oxidative Stress drug effects, Oxidative Stress radiation effects, Glutathione Peroxidase metabolism, Melatonin pharmacology, Testis radiation effects, Testis drug effects, Rats, Wistar, Radio Waves adverse effects
- Abstract
Background/aim: Primarily due to wireless communication devices, especially mobile phones, there has been a steady rise in the intensity of nonionizing radiofrequency radiation (RFR). In recent years, increased human health problems raised concerns about whether there is a positive relationship between intense exposure to RFR and public health. The present study aims to investigate the effects of GSM-like RFR exposure on the male reproductive system and the impact of melatonin treatment (synergistic, antagonist, or additive)., Materials and Methods: Thirty-six male Wistar Albino rats were used and separated into six groups: i. Control; ii. Sham; iii. RFR exposure; iv. Control-melatonin; v. Sham-melatonin; vi. Melatonin + RFR exposure. Animals were exposed to 2600 MHz RFR with electric (E) field levels of 21.74 V/m for 30 min per day, 5 days per week, for 4 weeks. All testicular tissue samples were evaluated under a light microscope for hematoxylin-eosin staining. Biochemical analyses were performed by measuring malondialdehyde, total nitric oxide, glutathione, and glutathione peroxidase levels. We evaluated the combined effects of prolonged RFR exposure and melatonin treatment on ROS-mediated structural changes in testicular tissues., Results: Results showed that reactive intermediates (malondialdehyde and total nitric oxide) increased significantly with RFR exposure, while the protective effect of melatonin effectively reduced the radical levels of the tissues. Histological evaluation revealed a decrease in cell population and connective tissue elements under RFR exposure, accompanied by marked edema in the testicular tissues., Conclusion: The structural and functional effects of prolonged RFR exposure might be ROS-based. Moreover, these adverse effects might be compensated with externally treated supplements. There is a need for new extensive research., Competing Interests: Conflict of interest: The authors declare that they have no conflicts of interest related to this paper., (© TÜBİTAK.)
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- 2024
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11. Radiation-induced Testicular Damage in Mice: Protective Effects of Apigenin Revealed by Histopathological Evaluation.
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Azmoonfar R, Mirzaei F, Najafi M, Varkeshi M, Ghazikhanlousani K, Momeni S, and Saber K
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- Animals, Male, Mice, Radiation Injuries, Experimental prevention & control, Radiation Injuries, Experimental pathology, Radiation Injuries, Experimental drug therapy, Spermatogenesis drug effects, Spermatogenesis radiation effects, Apigenin pharmacology, Testis drug effects, Testis pathology, Testis radiation effects, Radiation-Protective Agents pharmacology
- Abstract
Background: Radiation exposure poses a significant threat to reproductive health, particularly the male reproductive system. The testes, being highly sensitive to radiation, are susceptible to damage that can impair fertility and overall reproductive function. The study aims to investigate the radioprotective effects of apigenin on the testis through histopathological evaluation., Materials and Methods: This research involved utilizing a total of 40 mice, which were randomly divided into eight groups of five mice each. The groups were categorized as follows: A) negative control group, B, C, and D) administration of apigenin at three different doses (0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg) respectively, E) irradiation group, and F, H, and I) administration of apigenin at three different doses (0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg) in combination with irradiation. The irradiation procedure involved exposing the mice to a 2Gy X-ray throughout their entire bodies. Subsequently, histopathological assessments were conducted seven days after the irradiation process., Results: The findings indicated that radiation exposure significantly impacted the spermatogenesis system. This research provides evidence that administering apigenin to mice before ionizing radiation effectively mitigated the harmful effects on the testes. Apigenin demonstrated radioprotective properties, positively influencing various parameters, including the spermatogenesis process and the presence of inflammatory cells within the tubular spaces., Conclusion: Apigenin can provide effective protection for spermatogenesis, minimize the adverse effects of ionizing radiation, and safeguard normal tissues., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2024
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12. Dose-Dependent Testicular Injury and Recovery after Total-Body Irradiation in Rhesus Monkeys.
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Schaaf GW, Olson JD, Dugan GO, Pray BA, Cleary JA, and Cline JM
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- Humans, Animals, Male, Macaca mulatta, Dose-Response Relationship, Radiation, Testosterone, Testis radiation effects, Spermatogonia radiation effects
- Abstract
Testicular injury is a well-documented acute effect of radiation exposure, though little is known about recovery years after irradiation, especially at higher doses. We examined the testes from 143 irradiated and control male rhesus monkeys, who were part of the Radiation Late Effects Cohort over a four-year period. Irradiated animals were exposed to doses ranging from 3.5 to 8.5 Gy of total-body irradiation. The testes were assessed using computed tomography (CT) volumetry, serum testosterone, and histology for deceased members of the cohort. Irradiated animals exhibited dose-dependent testicular atrophy as well as decreased serum testosterone during the winter breeding season when compared to age-matched unirradiated controls. No significant difference in summer testosterone levels was observed. Volumetric and histologic evidence of testicular recovery was present approximately three years postirradiation for animals who received ≤8 Gy. The study demonstrates dose-dependent testicular injury after total-body irradiation and provides evidence for volumetric and spermatogonial recovery even at lethal doses of total-body irradiation in rhesus monkeys., (©2023 by Radiation Research Society. All rights of reproduction in any form reserved.)
- Published
- 2023
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13. Molecular Mechanism of Male Sterility Induced by 60 Co γ-Rays on Plutella xylostella (Linnaeus).
- Author
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Li S, Zhang K, Wen J, Zeng Y, Deng Y, Hu Q, and Weng Q
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- Male, Animals, Humans, Sperm Motility, Seeds, Testis radiation effects, Lepidoptera, Infertility, Male, Moths
- Abstract
Plutella xylostella (Linnaeus) is one of the notorious pests causing substantial loses to numerous cruciferous vegetables across many nations. The sterile insect technique (SIT) is a safe and effective pest control method, which does not pollute the environment and does not produce drug resistance. We used proteomics technology and bioinformatics analysis to investigate the molecular mechanisms responsible for the effects of different doses of radiation treatment on the reproductive ability of male P. xylostella . A total of 606 differentially expressed proteins (DEPs) were identified in the 200 Gy/CK group, 1843 DEPs were identified in the 400 Gy/CK group, and 2057 DEPs were identified in the 400 Gy/200 Gy group. The results showed that after 200 Gy irradiation, the testes resisted radiation damage by increasing energy supply, amino acid metabolism and transport, and protein synthesis, while transcription-related pathways were inhibited. After 400 Gy irradiation, the mitochondria and DNA in the testis tissue of P. xylostella were damaged, which caused cell autophagy and apoptosis, affected the normal life activities of sperm cells, and greatly weakened sperm motility and insemination ability. Meanwhile, Western blotting showed that irradiation affects tyrosine phosphorylation levels, which gradually decrease with increasing irradiation dose., Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
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14. Evaluation of incidental testicular dose with thermoluminescence dosimetry during prostate radiotherapy.
- Author
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Gul OV, Basaran H, and Inan G
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- Humans, Male, Prospective Studies, Prostate radiation effects, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted methods, Testis radiation effects, Prostatic Neoplasms radiotherapy, Radiotherapy, Intensity-Modulated methods
- Abstract
The aim of this study was to investigate incidental testicular doses during intensity modulated radiation therapy (IMRT) in patients treated with prostate radiotherapy only (PORT) and whole pelvis radiotherapy (WPRT). A total of 34 prostate cancer patients with intermediate and high risk were included in this prospective study. Each patient in the intermediate risk group received a total of 78 Gy in 39 fractions for prostate and seminal vesicles. In patients in the high risk group, 2 Gy daily fraction dose for pelvic lymphatics was given to 50 Gy, and then 78 Gy was given to prostate and seminal vesicles volumes. Treatment plans were created for all patients using the IMRT technique with 6MV. Testicular doses were measured for WPRT and PORT by thermoluminescence dosimetry (TLD) detectors placed on testis surface. Testicular doses measured for WPRT and PORT were compared. The isocenter to testicular distance for WPRT and PORT was 16.83-cm (13.20 to 18.80-cm) and 11.15 cm (9.10 to 13.00-cm), respectively. The mean testicular dose measurements of TPS and TLD per fraction during PORT were 2.41 cGy (1.95 to 3.60 cGy) and 3.70 cGy (2.80 to 5.10 cGy), respectively (p = 0.00). In WPRT irradiation, mean testicular dose values of TPS and TLD per fraction were measured as 3.85 cGy (2.00 to 5.70 cGy) and 5.85 cGy (4.25 to 7.55 cGy), respectively (p = 0.00). The cumulative mean scattered dose for PORT irradiation of 78 Gy in 39 fractions was 144.30 cGy. The mean cumulative dose received by the testis for the high-risk prostate patient was 228.15 cGy. There was a significant difference in testicular dose between WPRT and PORT irradiation. Testicular doses decreased significantly with increasing isocenter-testis distance. Incidental testicular dose during prostate radiotherapy can be significantly detrimental to spermatogenesis. Therefore, the testicles should be contoured as an organ at risk for the estimation of absorbed doses. The use of in vivo dosimetry is recommended for accurate measurement of testicular dose in radiotherapy of prostate cancer for men desiring continued fertility., (Copyright © 2022 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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15. Low-dose radiation-induced demethylation of 3β-HSD participated in the regulation of testosterone content.
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Huang CS, Qiu LZ, Yue L, Wang NN, Liu H, Deng HF, Ni YH, Ma ZC, Zhou W, and Gao Y
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- Animals, Dose-Response Relationship, Radiation, Male, Mice, Mice, Inbred C57BL, Demethylation, Gamma Rays adverse effects, Mesenchymal Stem Cells radiation effects, Multienzyme Complexes metabolism, Progesterone Reductase metabolism, Steroid Isomerases metabolism, Testis radiation effects, Testosterone metabolism
- Abstract
The effects of low-dose radiation (LDR, ≤0.1 Gy) on living organisms have been the hot areas of radiation biology but do not reach a definitive conclusion yet. So far, few studies have adequately accounted for the male reproductive system responses to LDR, particularly the regulation of testosterone content. Hence, this study was designed to evaluate the effects of LDR on Leydig cells and testicular tissue, especially the ability to synthesize testosterone. We found that less than 0.2-Gy
60 Co gamma rays did not cause significant changes in the hemogram index and the body weight; also, pathological examination did not find obvious structural alterations in testis, epididymis, and other radiation-sensitive organs. Consistently, the results from in vitro showed that only more than 0.5-Gy gamma rays could induce remarkable DNA damage, cycle arrest, and apoptosis. Notably, LDR disturbed the contents of testosterone in mice serums and culture supernatants of TM3 cells and dose dependently increased the expression of 3β-HSD. After cotreatment with trilostane (Tril), the inhibitor of 3β-HSD, increased testosterone could be partially reversed. Besides, DNA damage repair-related enzymes, including DNMT1, DNMT3B, and Sirt1, were increased in irradiated TM3 cells, accompanying by evident demethylation in the gene body of 3β-HSD. In conclusion, our results strongly suggest that LDR could induce obvious perturbation in the synthesis of testosterone without causing organic damage, during which DNA demethylation modification of 3β-HSD might play a crucial role and would be a potential target to prevent LDR-induced male reproductive damage., (© 2021 John Wiley & Sons, Ltd.)- Published
- 2022
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16. The potential adverse effect of 2.45 GHz microwave radiation on the testes of prenatally exposed peripubertal male rats.
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Andrašková S, Holovská K, Ševčíková Z, Andrejčáková Z, Tóth Š, Martončíková M, Račeková E, and Almášiová V
- Subjects
- Animals, Endothelial Cells, Female, Male, Pregnancy, Rats, Seminiferous Tubules radiation effects, Sertoli Cells, Microwaves adverse effects, Testis radiation effects
- Abstract
In utero development of organs is easily influenced by many environmental factors. The aim of this study was to elucidate the effect of microwave radiation (MR) at a frequency of 2.45 GHz and a specific absorption rate of 1.73 W/kg on intrauterine development of testis. Pregnant albino rats were exposed to whole-body MR for 2 hours per day throughout the pregnancy. Male offspring (n=12, age 35 days) were not exposed to MR after birth. The study revealed that MR applied in utero induced apparent structural changes in the testes, such as irregular shape of seminiferous tubules, significant decrease in the diameter of seminiferous tubules (p<0.05) and in the height of the germinal epithelium (p<0.01), disorganisation of germ cells, desquamations of immature germ cells, formation of giant multinucleated cells, and significant (p<0.01) expansion of the interstitium. At the level of transmission electron microscopy, there were observed basement membrane irregularities in seminiferous tubules, vacuolation of the cytoplasm and adversely affected organelles in Sertoli cells, germ cells, Leydig cells, peritubular and endothelial cells. The tight junctions between adjacent Sertoli cells were often incomplete, and necrotizing germ cells were more numerous in experimental animals compared to controls. Enhanced necrotizations of germ cells proved by a Fluoro Jade C method, and declined germ cells proliferation confirmed by proliferating cell nuclear antigen analysis, were detected in MR exposed animals. Our results revealed that the prenatal exposure to MR had an adverse effect on the postnatal testicular development in rats.
- Published
- 2022
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17. Human Amnion Membrane-Derived Mesenchymal Stem Cells and Conditioned Medium Can Ameliorate X-Irradiation-Induced Testicular Injury by Reducing Endoplasmic Reticulum Stress and Apoptosis.
- Author
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Cetinkaya-Un B, Un B, Akpolat M, Andic F, and Yazir Y
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- Animals, Culture Media, Conditioned, Female, Humans, Male, Rats, Amnion cytology, Apoptosis radiation effects, Endoplasmic Reticulum Stress radiation effects, Infertility, Male etiology, Infertility, Male therapy, Mesenchymal Stem Cell Transplantation, Testis radiation effects
- Abstract
Today, infertility affects 15% of couples and half of this rate is due to reproductive problems in men. Radiation-induced damage to the testicles causes sterility depending on the dose. Radiation causes endoplasmic reticulum (ER) stress and ER stress induces apoptosis. In this study, the effect of human amniotic membrane-derived mesenchymal stem cells (hAMSCs) and conditioned medium (hAMSCs-CM) on testicular damage induced by ionizing radiation is aimed to be elucidated through ER stress and apoptosis mechanisms. Six gray scrotal irradiation was used to create a testicular injury model. hAMSCs isolated and characterized with immunofluorescence and flow cytometry, while 2.5 × 10
5 hAMSCs were transplanted into testis and hAMSCs-CM was applied. Fertility assessment was performed. Expressions of ER stress markers GRP78, Ire1, Chop and Caspase-12, and Caspase-3 were determined. TUNEL was performed. Serum FSH, LH, and testosterone were measured. After hAMSC transplantation and administration of hAMSCs-CM, offsprings were obtained. Seminiferous tubule diameter and seminiferous epithelial height increased. The expression of GRP78, IRE1α, CHOP, Caspase-12, and Caspase-3 decreased. Percentages of tunel positive cells decreased. While FSH and LH levels decreased, testosterone increased. After irradiation, both hAMSCs transplantation and paracrine activity of hAMSCs may have a role in reducing ER stress by suppressing the UPR response. Decrease in FSH and LH and increase in testosterone level after MSCs transplantation may have contributed to the improvement of spermatogenesis. Thus, it can be said that MSCs derived from human amniotic membrane can improve ionized radiation-induced testicular damage by reducing ER stress and apoptosis., (© 2021. Society for Reproductive Investigation.)- Published
- 2022
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18. KR-31831 improves survival and protects hematopoietic cells and radiosensitive tissues against radiation-induced injuries in mice.
- Author
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Lee JH, Yi H, Lee JH, Seo HW, Oh KS, and Lee BH
- Subjects
- Animals, Bone Marrow Cells drug effects, Bone Marrow Cells metabolism, Bone Marrow Cells radiation effects, Intestines drug effects, Intestines radiation effects, Male, Mice, Inbred C57BL, Radiation Injuries genetics, Testis drug effects, Testis radiation effects, Transcriptome drug effects, Mice, Benzopyrans therapeutic use, Imidazoles therapeutic use, Radiation Injuries drug therapy, Radiation-Protective Agents therapeutic use, Whole-Body Irradiation adverse effects
- Abstract
This study explored the radioprotective effects and possible underlying mechanisms of KR-31831 against radiation-induced injury in a mouse model. KR-31831 (30 and 50 mg/kg) was administered to mice 24 h and 30 min before exposure to a single lethal or sublethal dose of whole-body irradiation (WBI) (7 or 4 Gy, respectively). These animals were then evaluated for changes in mortality, various hematological and biochemical parameters, and histological features in response to these treatments. In addition, RNA sequencing was used to profile the radiation-induced transcriptomic response in the bone marrow cells. The results showed that KR-31831 dose-dependently prolonged the 30-day survival period and prevented damage to radiation-sensitive organs, such as the intestine and testis, in response to WBI. Damage to the hematopoietic system was also notably improved in the KR-31831-treated mice, as evidenced by an increase in bone marrow and peripheral blood cells, as well as recovery of the histopathological characteristics of the bone marrow. These protective effects were achieved, at least in part, via the suppression of radiation-induced increases in apoptotic cell death and erythropoietin levels in the plasma. Furthermore, the gene expression profiles of the bone marrow cells of the WBI-treated mice suggested that KR-31831 upregulates the expression of the genes involved in regulating apoptosis and modulating the immune response, both of which are required for protecting the bone marrow. These results suggest the potential therapeutic efficacy of KR-31831 for protection against radiation-induced injury., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2022
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19. Changes in Expression of Specific mRNA Transcripts after Single- or Re-Irradiation in Mouse Testes.
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Nagahori K, Qu N, Kuramasu M, Ogawa Y, Kiyoshima D, Suyama K, Hayashi S, Sakabe K, Yoshimoto T, and Itoh M
- Subjects
- Animals, Gene Expression Profiling, Male, Mice, Mice, Inbred C57BL, RNA, Messenger genetics, Sertoli Cells radiation effects, Testis radiation effects, Gene Expression Regulation radiation effects, RNA, Messenger metabolism, Re-Irradiation methods, Sertoli Cells metabolism, Spermatogenesis, Testis metabolism
- Abstract
Alkylating agents and irradiation induce testicular damage, which results in prolonged azoospermia. Even very low doses of radiation can significantly impair testis function. However, re-irradiation is an effective strategy for locally targeted treatments and the pain response and has seen important advances in the field of radiation oncology. At present, little is known about the relationship between the harmful effects and accumulated dose of irradiation derived from continuous low-dose radiation exposure. In this study, we examined the levels of mRNA transcripts encoding markers of 13 markers of germ cell differentiation and 28 Sertoli cell-specific products in single- and re-irradiated mice. Our results demonstrated that re-irradiation induced significantly decreased testicular weights with a significant decrease in germ cell differentiation mRNA species ( Spo11 , Tnp1 , Gfra1, Oct4, Sycp3, Ddx4 , Boll, Crem, Prm1, and Acrosin ). In the 13 Sertoli cell-specific mRNA species decreased upon irradiation, six mRNA species ( Claudin-11, Espn, Fshr, GATA1, Inhbb , and Wt1 ) showed significant differences between single- and re-irradiation. At the same time, different decreases in Sertoli cell-specific mRNA species were found in single-irradiation ( Aqp8 , Clu , Cst12 , and Wnt5a ) and re-irradiation ( Tjp1, occludin, ZO -1, and ZO -2) mice. These results indicate that long-term aspermatogenesis may differ after single- and re-irradiated treatment.
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- 2022
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20. Radioprotective Effect of Febuxostat Against Testicular Damage Induced by Ionizing Radiation in Mice.
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Amiri FT, Raeispour M, Farzipour S, and Hosseinimehr SJ
- Subjects
- Animals, Febuxostat pharmacology, Humans, Male, Mice, Radiation, Ionizing, Radiopharmaceuticals pharmacology, Testis pathology, Testis radiation effects, Prostatic Neoplasms drug therapy, Radiation-Protective Agents pharmacology, Radiation-Protective Agents therapeutic use
- Abstract
Background: The testis is one of the most radiosensitive tissues in pelvic radiotherapy, especially in prostate cancer. Febuxostat (FBX), as an inhibitor of xanthine oxidase, has anti-inflammatory, antioxidant, and anti-apoptosis properties., Objectives: The aim of this research was to survey the protective effect of FBX against irradiation (IR)-induced testis damage via the attenuation of oxidative stress., Methods: Male adult mice were randomly assigned into eight groups: control, FBX with three doses of 5, 10, and 15 mg/kg, IR with 6 Gy, IR + FBX (IR + FBX in three doses), respectively. In the IR + FBX groups, FBX was administrated for 8 consecutive days, and then mice were exposed to IR at a dose of 6 Gy on the 9th day. One day after irradiation, biochemical parameters were evaluated in the testis of animals, while histopathological assessment had been performed on 14th day., Results: Irradiation led to the induction of testicular toxicity. FBX significantly protected histopathological alterations and decreased oxidative stress parameters in irradiated testis. Besides, FBX increased the diameter and germinal epithelial thickness of seminiferous tubules and Johnson's score in irradiated mice., Conclusion: Data showed that FBX markedly protected testicular injury induced by IR by inhibiting oxidative stress and may be considered as an infertility inhibitor in cancer patients, especially prostate cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2022
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21. Effects of Sargassum virgatum extracts on the testicular measurements, genomic DNA and antioxidant enzymes in irradiated rats.
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Semaida AI, El-Khashab MA, Saber AA, Hassan AI, and Elfouly SA
- Subjects
- Animals, Antioxidants metabolism, Antioxidants pharmacology, Catalase metabolism, DNA, Glutathione metabolism, Glutathione Peroxidase metabolism, Male, Oxidative Stress radiation effects, Plant Extracts pharmacology, Rats, Rats, Wistar, Semen Analysis, Superoxide Dismutase metabolism, Testis radiation effects, Infertility, Male, Sargassum metabolism
- Abstract
Background: Oxidative stress and reactive oxygen species (ROS) are primarily responsible for the development of male infertility after exposure to γ-irradiation. The present work aimed to assess the ameliorative and therapeutic roles of the aqueous and ethanolic extracts of the edible seaweed Sargassum virgatum ( S. virgatum ) on spermatogenesis and infertility in γ-irradiated Wistar rats., Materials and Methods: Induction of infertility was performed by exposing the rats to
137 Cs-gamma rays, using a single dose of 3.5 Gy. γ-irradiated rats were given the S. virgatum ethanolic ( S. virgatum -EtOH) and aqueous extracts intraperitoneally on a daily base for two consecutive weeks at doses of 100 and 400 mg/kg body weight (b.wt.) for each seaweed extract. Morphometric data of the testes, semen quality indices, antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx), and deoxyribonucleic acid (DNA) fragmentation were assessed. The results obtained were taken during two-time intervals of 15 and 60 days from the commencement of the algal treatments. In vitro antioxidant assays and polyphenolic compounds of S. virgatum were characterized., Results: Significant negative changes in the semen quality and morphometric data of the testes, as well as remarkable DNA fragmentation, were detected in the irradiated rats compared to the control. The levels of the endogenous antioxidant enzymes (SOD, CAT, GSH, and GPx) were also significantly diminished. Nonetheless, treatments of γ-irradiated rats with the S. virgatum -EtOH and aqueous extracts significantly improved the above-mentioned enzymes, in addition to noteworthy amendments in the dimensions of the testes, the semen quality, as well as the DNA structure., Conclusions: The ameliorative potency of S. virgatum to cure γ-irradiation-induced male infertility, particularly 400 mg/kg ethanolic extract for 60 days, is the result of the consistent therapeutic interventions of its potent antioxidant and anti-apoptotic polyphenols, particularly protocatechuic, p -hydroxybenzoic, rosmarinic, chlorogenic, cinnamic and gentisic acids, as well as the flavonoids catechin, hesperidin, rutin and quercetin. Besides its high-value nutraceutical importance, S. virgatum could be a natural candidate for developing well-accepted radioprotectant products capable of treating γ-irradiation-induced male infertility.- Published
- 2022
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22. Association between occupational testicular radiation exposure and lower male sex ratio of offspring among orthopedic surgeons.
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Hijikata Y, Nakahara M, Kusumegi A, Morii J, Okubo N, Hatano N, and Takahashi Y
- Subjects
- Case-Control Studies, Child, Child, Preschool, Data Collection, Female, Humans, Infant, Infant, Newborn, Japan, Male, Multivariate Analysis, Probability, Sex Ratio, Spermatids drug effects, Spermatogonia drug effects, Surveys and Questionnaires, Occupational Exposure, Orthopedic Surgeons, Paternal Exposure, Testis radiation effects
- Abstract
Background: Exposure to occupational radiation can lower the male sex ratio. However, specific radiation exposure to the testes has not been evaluated., Objective: This study aimed to examine the association between testicular radiation exposure and lower male sex ratio in children., Methods: A comprehensive questionnaire survey was administered to 62 full-time male doctors with children aged < 10 years at 5 hospitals. Based on the possibility of testicular radiation exposure 1 year before the child's birth, participants were assigned to 3 groups as follows: RT (orthopedic surgery), RNT (cardiology/neurosurgery), and N (others). Intergroup differences in the proportion of female children were ascertained, and the female sex ratio (number of female/total number) of each group was compared against the standard value of 0.486. Multivariate logistic regression analysis with a generalized estimating equation was used to model the effects on the probability of female birth while controlling for the correlation among the same fathers., Results: The study population included 62 fathers and 109 children, 49 were female: 19/27, 11/30, and 19/52 in the RT, RNT, and N group, respectively; the RT group had the highest proportion of females (p = 0.009). The p values for comparisons with the standard sex ratio (0.486) were 0.02, 0.19, and 0.08 for the RT, RNT, and N groups, respectively. Based on the N group, the adjusted odds ratios for the child to be female were 4.40 (95% confidence interval 1.60-2.48) and 1.03 (0.40-2.61) for the RT and RNT groups, respectively., Conclusions: Our results imply an association between testicular radiation exposure and low male sex ratio of offspring. Confirmatory evidence is needed from larger studies which measure the pre-conceptional doses accumulated in various temporal periods, separating out spermatogonial and spermatid effects., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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23. Differential Effects of Low and High Radiation Dose Rates on Mouse Spermatogenesis.
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Bae MJ, Kang MK, Kye YU, Baek JH, Sim YJ, Lee HJ, Kang YR, Jo WS, Kim JS, and Lee CG
- Subjects
- Animals, Dose-Response Relationship, Radiation, Gamma Rays, Male, Mice, Models, Animal, Radiation Dosage, Spermatids cytology, Spermatids radiation effects, Spermatogonia cytology, Spermatogonia radiation effects, Spermatozoa cytology, Spermatozoa radiation effects, Testis cytology, Spermatogenesis radiation effects, Testis radiation effects
- Abstract
The adverse effects of radiation are proportional to the total dose and dose rate. We aimed to investigate the effects of radiation dose rate on different organs in mice. The mice were subjected to low dose rate (LDR, ~3.4 mGy/h) and high dose rate (HDR, ~51 Gy/h) radiation. LDR radiation caused severe tissue toxicity, as observed in the histological analysis of testis. It adversely influenced sperm production, including sperm count and motility, and induced greater sperm abnormalities. The expression of markers of early stage spermatogonial stem cells, such as Plzf, c-Kit, and Oct4, decreased significantly after LDR irradiation, compared to that following exposure of HDR radiation, in qPCR analysis. The compositional ratios of all stages of spermatogonia and meiotic cells, except round spermatid, were considerably reduced by LDR in FACS analysis. Therefore, LDR radiation caused more adverse testicular damage than that by HDR radiation, contrary to the response observed in other organs. Therefore, the dose rate of radiation may have differential effects, depending on the organ; it is necessary to evaluate the effect of radiation in terms of radiation dose, dose rate, organ type, and other conditions.
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- 2021
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24. Circadian effects of ionizing radiation on reproductive function and clock genes expression in male mouse.
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Qin F, Liu N, Nie J, Shen T, Xu Y, Pan S, Pei H, and Zhou G
- Subjects
- ARNTL Transcription Factors genetics, Acid Phosphatase, Animals, CLOCK Proteins genetics, Epididymis radiation effects, Glucosephosphate Dehydrogenase, L-Iditol 2-Dehydrogenase, L-Lactate Dehydrogenase, Male, Mice, Mice, Inbred C57BL, Models, Animal, Nuclear Receptor Subfamily 1, Group F, Member 1 genetics, Nuclear Receptor Subfamily 1, Group F, Member 2 genetics, Nuclear Receptor Subfamily 1, Group F, Member 3 genetics, RNA, Messenger genetics, Sperm Motility radiation effects, Spermatozoa radiation effects, Testis enzymology, Testis radiation effects, Circadian Rhythm radiation effects, Gene Expression radiation effects, Genitalia, Male radiation effects, Radiation Exposure, Radiation, Ionizing, Reproductive Physiological Phenomena radiation effects
- Abstract
Background: Exposure to the ionizing radiation (IR) encountered outside the magnetic field of the Earth poses a persistent threat to the reproductive functions of astronauts. The potential effects of space IR on the circadian rhythms of male reproductive functions have not been well characterized so far., Methods: Here, we investigated the circadian effects of IR exposure (3 Gy X-rays) on reproductive functional markers in mouse testicular tissue and epididymis at regular intervals over a 24-h day. For each animal, epididymis was tested for sperm motility, and the testis tissue was used for daily sperm production (DSP), testosterone levels, and activities of testicular enzymes (glucose-6-phosphate dehydrogenase (G6PDH), sorbitol dehydrogenase (SDH), lactic dehydrogenase (LDH), and acid phosphatase (ACP)), and the clock genes mRNA expression such as Clock, Bmal1, Ror-α, Ror-β, or Ror-γ., Results: Mice exposed to IR exhibited a disruption in circadian rhythms of reproductive markers, as indicated by decreased sperm motility, increased daily sperm production (DSP), and reduced activities of testis enzymes such as G6PDH, SDH, LDH, and ACP. Moreover, IR exposure also decreased mRNA expression of five clock genes (Clock, Bmal1, Ror-α, Ror-β, or Ror-γ) in testis, with alteration in the rhythm parameters., Conclusion: These findings suggested potential health effects of IR exposure on reproductive functions of male astronauts, in terms of both the daily overall level as well as the circadian rhythmicity., (© 2021. The Author(s).)
- Published
- 2021
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25. Modulatory effects of Punica granatum L juice against 2115 MHz (3G) radiation-induced reproductive toxicity in male Wistar rat.
- Author
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Gautam R, Priyadarshini E, Nirala JP, Meena R, and Rajamani P
- Subjects
- Animals, Male, Rats, Rats, Wistar, Testis pathology, Fruit and Vegetable Juices, Pomegranate chemistry, Radiation Injuries, Experimental therapy, Radiation-Protective Agents pharmacology, Testis radiation effects
- Abstract
Advancements in telecommunication sector result in increasing exposure to electromagnetic (EM) radiation, which has been correlated with incidence of male infertility. Therefore, the present study focused on analyzing the consequence of EM radiation (2115 MHz) exposure on the reproductive system of male Wistar rats. Besides, the antioxidant protective effect of Punica granatum juice was also evaluated. For experimental analysis, rats were divided into five groups (control, sham exposed, exposed, herbal plus exposed, and herbal only). Individual group consisted of 6 rats which were exposed to radiation for 45 days (2 h/day). The herbal-treated groups were given 1 ml of Punica granatum extract orally. Various parameters such as organ to body ratio, sperm count, motility, viability, and testis histopathology were studied. Furthermore, oxidative stress parameters and free radical generation were analyzed. The exposed group showed changes in sperm parameters along with decrease in seminiferous tubule diameter. On the contrary, herbal-exposed group showed enhanced sperm count, increased motility, and viability in comparison to exposed group. Histopathology studies also revealed the protective role of herbal juice. Significant alteration in oxidative parameters along with an enhanced free radical generation in exposed group and reduction in herbal groups was observed. The results thus indicate that continuous exposure to EM radiation can lead to oxidative stress which induces biochemical changes in rat sperms. However, Punica granatum extract has a protective role against oxidative damage induced by EM radiation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2021
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26. Postpubertal spermatogonial stem cell transplantation restores functional sperm production in rhesus monkeys irradiated before and after puberty.
- Author
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Shetty G, Mitchell JM, Lam TNA, Phan TT, Zhang J, Tailor RC, Peters KA, Penedo MC, Hanna CB, Clark AT, Orwig KE, and Meistrich ML
- Subjects
- Animals, Cryopreservation, Gonadotropin-Releasing Hormone antagonists & inhibitors, Hormone Antagonists administration & dosage, Macaca mulatta, Male, Radiation Injuries, Experimental physiopathology, Seminiferous Tubules, Spermatozoa radiation effects, Testis physiopathology, Testis radiation effects, Adult Germline Stem Cells transplantation, Puberty radiation effects, Radiation Injuries, Experimental therapy, Spermatogenesis radiation effects, Stem Cell Transplantation
- Abstract
Background: Cancer treatment of prepubertal patients impacts future fertility due to the abolition of spermatogonial stem cells (SSCs). In macaques, spermatogenesis could be regenerated by intratesticular transplantation of SSCs, but no studies have involved cytotoxic treatment before puberty and transplantation after puberty, which would be the most likely clinical scenario., Objectives: To evaluate donor-derived functional sperm production after SSC transplantation to adult monkeys that had received testicular irradiation during the prepubertal period., Materials and Methods: We obtained prepubertal testis tissue by unilaterally castrating six prepubertal monkeys and 2 weeks later irradiated the remaining testes with 6.9 Gy. However, because spermatogenic recovery was observed, we irradiated them again 14 months later with 7 Gy. Three of the monkeys were treated with GnRH-antagonist (GnRH-ant) for 8 weeks. The cryopreserved testis cells from the castrated testes were then allogeneically transplanted into the intact testes of all monkeys. Tissues were harvested 10 months later for analyses., Results: In three of the six monkeys, 61%, 38%, and 11% of the epididymal sperm DNA were of the donor genotype. The ability to recover donor-derived sperm production was not enhanced by the GnRH-ant pretreatment. However, the extent of filling seminiferous tubules during the transplantation procedure was correlated with the eventual production of donor spermatozoa. The donor epididymal spermatozoa from the recipient with 61% donor contribution were capable of fertilizing rhesus eggs and forming embryos. Although the transplantation was done into the rete testis, two GnRH-ant-treated monkeys, which did not produce donor-derived epididymal spermatozoa, displayed irregular tubular cords in the interstitium containing testicular spermatozoa derived from the transplanted donor cells., Discussion and Conclusion: The results further support that sperm production can be restored in non-human primates from tissues cryopreserved prior to prepubertal and post-pubertal gonadotoxic treatment by transplantation of these testicular cells after puberty into seminiferous tubules., (© 2021 American Society of Andrology and European Academy of Andrology.)
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- 2021
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27. Potential influence of prenatal 2.45 GHz radiofrequency electromagnetic field exposure on Wistar albino rat testis.
- Author
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Almášiová V, Holovská K, Andrašková S, Cigánková V, Ševčíková Z, Raček A, Andrejčáková Z, Beňová K, Tóth Š, Tvrdá E, Molnár J, and Račeková E
- Subjects
- Animals, Female, Leydig Cells pathology, Male, Rats, Rats, Wistar, Seminiferous Tubules radiation effects, Sertoli Cells pathology, Testis embryology, Testis pathology, Electromagnetic Fields adverse effects, Testis radiation effects
- Abstract
An ever-increasing use of wireless devices over the last decades has forced scientists to clarify their impact on living systems. Since prenatal development is highly sensitive to numerous noxious agents, including radiation, we focused on the assessment of potential adverse effects of microwave radiation (MR) on testicular development. Pregnant Wistar albino rats (3 months old, weighing 282±8 g) were exposed to pulsed MR at a frequency of 2.45 GHz, mean power density of 2.8 mW/cm², and a specific absorption rate of 1.82 W/kg for 2 hours/day throughout pregnancy. Male offspring were no longer exposed to MR following birth. Samples of biological material were collected after reaching adulthood (75 days). In utero MR exposure caused degenerative changes in the testicular parenchyma of adult rats. The shape of the seminiferous tubules was irregular, germ cells were degenerated and often desquamated. The diameters of the seminiferous tubules and the height of the germinal epithelium were significantly decreased (both at ∗∗p<0.01), while the interstitial space was significantly increased (∗∗p<0.01) when compared to the controls. In the group of rats prenatally exposed to MR, the somatic and germ cells were rich in vacuoles and their organelles were often altered. Necrotizing cells were more frequent and empty spaces between Sertoli cells and germ cells were observed. The Leydig cells contained more lipid droplets. An increased Fluoro Jade - C and superoxide dismutase 2 positivity was detected in the rats exposed to MR. Our results confirmed adverse effects of MR on testicular development.
- Published
- 2021
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28. Radiation-induced abscopal reproductive effect is driven by TNF-α/p38 MAPK/Rac1 axis in Sertoli cells.
- Author
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Hu S, Zhu L, Song Y, Zhao X, Chen Q, Pan Y, Zhang J, Bai Y, Zhang H, and Shao C
- Subjects
- Animals, Blood-Testis Barrier metabolism, Blood-Testis Barrier radiation effects, MAP Kinase Signaling System radiation effects, Male, Mice, Mice, Inbred C57BL, Testis metabolism, Testis radiation effects, Neuropeptides metabolism, Reproduction radiation effects, Sertoli Cells metabolism, Sertoli Cells radiation effects, Tumor Necrosis Factor-alpha metabolism, p38 Mitogen-Activated Protein Kinases metabolism, rac1 GTP-Binding Protein metabolism
- Abstract
Rationale: Radiotherapy has become a mainstay for tumor management, and more than 50% of patients with thoracic tumor need to be treated with radiotherapy. However, the potential adverse effects of thoracic radiotherapy on the reproductive system remain elusive. Methods: Western blot analysis, immunofluorescence assay and transmission electron microscopy (TEM) analysis were performed to investigate the integrity of blood-testis barrier (BTB) in male mice after hypofractionated irradiation (IR) on the right thorax. RNA sequencing, co-immunoprecipitation (IP), Duolink PLA and inhibitor experiments were carried out to demonstrate the molecular mechanisms of the BTB dynamics changes and the subsequent reproductive effect. Results: It was found that the hypofractionated IR on right thorax evoked ultrastructural destruction in distant testes, and thus caused radiation-induced abscopal reproductive effect (RIARE) in male mice. Mechanistically, thoracic IR induced significant nuclear translocation of Rac Family Small GTPase 1 (Rac1) in abscopal Sertoli cells, which closely correlated with the activation of TNF-α/p38 mitogen activated protein kinase (MAPK) pathway. Of note, YWHAZ, a critical polarity protein, was found to be co-localized with Rac1 in Sertoli cells, and this interaction was indispensable for thoracic IR-induced Rac1 nuclear translocation and subsequent degradation of BTB-associated proteins. Conclusions: Our findings imply for the first time that YWHAZ-mediated Rac1 nuclear translocation plays central roles in RIARE, and TNF-α/p38 MAPK/Rac1 axis can be employed as a therapeutic target against RIARE for young male patients receiving hypofractionated radiotherapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
- Published
- 2021
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29. Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms.
- Author
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Rossi G, Placidi M, Castellini C, Rea F, D'Andrea S, Alonso GL, Gravina GL, Tatone C, Di Emidio G, and D'Alessandro AM
- Subjects
- Animals, Autophagy drug effects, Autophagy radiation effects, Carotenoids therapeutic use, Catalase metabolism, Cells, Cultured, Down-Regulation, ELAV-Like Protein 1 metabolism, Fertility radiation effects, Gene Expression Regulation, Developmental drug effects, Gene Expression Regulation, Developmental radiation effects, Immunohistochemistry, In Vitro Techniques, Male, Mice, Microtubule-Associated Proteins metabolism, Oxidative Stress drug effects, Oxidative Stress radiation effects, Poly (ADP-Ribose) Polymerase-1 metabolism, Proliferating Cell Nuclear Antigen metabolism, Puberty radiation effects, Seminiferous Tubules cytology, Seminiferous Tubules drug effects, Seminiferous Tubules radiation effects, Sirtuin 1 metabolism, Superoxide Dismutase metabolism, Testis radiation effects, Up-Regulation, Vitamin A pharmacology, Vitamin A therapeutic use, X-Rays, Carotenoids pharmacology, Fertility drug effects, Puberty drug effects, Radiation Injuries drug therapy, Testis drug effects, Vitamin A analogs & derivatives
- Abstract
Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 μM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.
- Published
- 2021
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30. Effects of Continuous In Utero Low- and Medium-Dose-Rate Gamma-Ray Exposure on Fetal Germ Cells.
- Author
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Nakahira R, Ayabe Y, Braga-Tanaka I, Tanaka S, and Komura JI
- Subjects
- Animals, Cell Survival radiation effects, Dose-Response Relationship, Radiation, Female, Fetus physiopathology, Germ Cells pathology, Male, Mice, Ovary physiopathology, Ovary radiation effects, Radiation Dosage, Radiation Protection, Testis physiopathology, Testis radiation effects, Chromosome Aberrations radiation effects, Fetus radiation effects, Gamma Rays adverse effects, Germ Cells radiation effects
- Abstract
The effects of radiation exposure on germ cells and the gonads have been well studied at acute high-dose exposures, but the effects of chronic low-dose-rate (LDR) irradiation, particularly relevant for radiation protection, on germ cells and the gonads are largely unknown. Our previous study revealed that chronic exposure of mice to medium-dose-rate (MDR, 200 or 400 mGy/day) gamma-rays in utero for the entire gestation period (18 days) induced only a mild degree of general growth retardation, but with very drastic effects on the gonads and germ cells. In the current study, we further investigated the histomorphological changes in the gonads and the number of germ cells from gestation day (GD) 18 fetuses irradiated with MDR throughout the entire gestation period. The germ cells in the testes and ovaries of the MDR-irradiated fetuses were almost obliterated. Gestation day 18 fetuses exposed to LDR (20 mGy/day) radiation for the entire gestation period showed decreases in the number of the germ cells, which were not statistically significant or only marginally significant at most. Further investigations on the effects of LDR irradiation in utero using more sensitive methods are necessary., (©2021 by Radiation Research Society. All rights of reproduction in any form reserved.)
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- 2021
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31. Morphological reproductive characteristics of testes and fertilization capacity of cryopreserved sperm after the Fukushima accident in raccoon (Procyon lotor).
- Author
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Komatsu K, Iwasaki T, Murata K, Yamashiro H, Goh VST, Nakayama R, Fujishima Y, Ono T, Kino Y, Simizu Y, Takahashi A, Shinoda H, Ariyoshi K, Kasai K, Suzuki M, Palmerini MG, Belli M, Macchiarelli G, Oka T, Fukumoto M, Yoshida MA, Nakata A, and Miura T
- Subjects
- Animals, Cesium Radioisotopes analysis, Cryopreservation veterinary, Female, Fertilization in Vitro, Introduced Species, Japan, Male, Mice, Inbred ICR, Raccoons anatomy & histology, Semen Preservation veterinary, Spermatogenesis radiation effects, Testis physiology, Testis ultrastructure, Mice, Cesium Radioisotopes adverse effects, Fukushima Nuclear Accident, Raccoons physiology, Testis radiation effects
- Abstract
Since the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, we have established an archive system of livestock and wild animals from the surrounding ex-evacuation zone. Wildlife within the alert zone have been exposed to low-dose-rate (LDR) radiation for a long continuous time. In this study, we analysed the morphological characteristics of the testes and in vitro fertilization (IVF) capacity of cryopreserved sperm of racoons from the ex-evacuation zone of the FDNPP accident. The radioactivity of caesium-137 (
137 Cs) was measured by gamma-ray spectrometry, and the measured radioactivity concentration was 300-6,630 Bq/kg in the Fukushima raccoons. Notably, normal spermatogenesis was observed in the seminiferous tubules of the testes, with the germinal epithelium composed of a spermatogenic cell lineage with no evident ultrastructural alterations; freeze-thawing sperm penetration ability was confirmed using the interspecific zona pellucida-free mouse oocytes IVF assays. This study revealed that the chronic and LDR radiation exposure associated with the FDNPP accident had no adverse effect on the reproductive characteristics and functions of male raccoons., (© 2020 Wiley-VCH GmbH.)- Published
- 2021
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32. A comparison of radiotherapy treatment planning techniques in patients with rectal cancers by analyzing testes doses.
- Author
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Duman E, Bilek Y, and Ceyran G
- Subjects
- Chemoradiotherapy, Humans, Male, Neoadjuvant Therapy, Organs at Risk pathology, Organs at Risk radiation effects, Radiotherapy Dosage, Radiotherapy, Conformal methods, Radiotherapy, Intensity-Modulated methods, Rectal Neoplasms drug therapy, Rectal Neoplasms pathology, Testis pathology, Radiotherapy Planning, Computer-Assisted methods, Rectal Neoplasms radiotherapy, Testis radiation effects
- Abstract
Purpose: To evaluate the target volume (TV) and critical organ doses with priority of testes with the comparison of conformal radiotherapy (CRT), dynamic intensity-modulated radiotherapy (DIMRT), and volumetric modulated arc therapy (VMAT) techniques., Materials and Methods: CRT, DIMRT, and VMAT techniques were generated on computed tomography images in prone position of 10 male patients with distal rectal cancer. Conformity index (CI), heterogeneity index (HI), treatment time, and monitor units were examined; dose-volume-histograms (DVHs) for the TV and the organs at risk (OARs) were evaluated., Results: Target dose coverage of all treatment plans was similar. HI and CI values for DIMRT and VMAT were closer to "1" compared to CRT. DVH parameters for OARs were decreased with DIMRT and VMAT compared to CRT. The percent volume (V
x ) of 3 Gy dose of testes was 62.01% (±25.45%), 42.68% (±16.42%), and 35.89% (±14.97%) in the CRT, DIMRT, and VMAT techniques, respectively. V3 of testes decreased with VMAT compared to CRT and DIMRT (P = 0.008 and P = 0.051, respectively)., Conclusion: Modern radiotherapy techniques are superior to conformal techniques in planning quality parameters and sparing OARs. DIMRT and VMAT could be considered instead of CRT in the desire to preserve fertility of patients with rectal cancer., Competing Interests: None- Published
- 2021
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33. Meiotic susceptibility for induction of sperm with chromosomal aberrations in patients receiving combination chemotherapy for Hodgkin lymphoma.
- Author
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Frias S, Van Hummelen P, Meistrich ML, and Wyrobek AJ
- Subjects
- Adult, Adult Germline Stem Cells drug effects, Adult Germline Stem Cells radiation effects, Cancer Survivors, Chemoradiotherapy adverse effects, Chemoradiotherapy methods, Chromosome Aberrations radiation effects, Cohort Studies, Fertility Preservation, Humans, In Situ Hybridization, Fluorescence methods, Male, Meiosis radiation effects, Mitoxantrone adverse effects, Mutagenesis drug effects, Mutagenesis radiation effects, Organ Sparing Treatments adverse effects, Organ Sparing Treatments methods, Organs at Risk radiation effects, Prednisone adverse effects, Radiotherapy Dosage, Spermatogenesis drug effects, Spermatogenesis radiation effects, Spermatozoa physiology, Spermatozoa radiation effects, Testis drug effects, Testis radiation effects, Time Factors, Vinblastine adverse effects, Vincristine adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Chromosome Aberrations drug effects, Hodgkin Disease therapy, Meiosis drug effects, Semen Analysis methods, Spermatozoa drug effects
- Abstract
Improvements in survival rates with gonad-sparing protocols for childhood and adolescence cancer have increased the optimism of survivors to become parents after treatment. Findings in rodents indicate that chromosomal aberrations can be induced in male germ cells by genotoxic exposures and transmitted to offspring and future generations with effects on development, fertility and health. Thus, there is a need for effective technologies to identify human sperm carrying chromosomal aberrations to assess the germ-line risks, especially for cancer survivors who have received genotoxic therapies. The time-dependent changes in the burden of sperm carrying structural chromosomal aberrations were assessed for the first time in a cancer setting, using the AM8 sperm FISH protocol which simultaneously detects abnormalities in chromosomal structure and number in sperm. Nine Hodgkin lymphoma (HL) patients provided 20 semen samples before, during, and after NOVP therapy (Novantrone, Oncovin, Velban and Prednisone) and radiation therapy that produced scattered gonadal doses from <0.05 to 0.6 Gy. Late meiosis was found to be the most sensitive to NOVP treatment for the production of sperm with chromosomal abnormalities, both in structure and number. Earlier stages of spermatogenesis were less sensitive and there was no evidence that therapy-exposed stem cells resulted in increased frequencies of sperm with abnormalities in chromosomal structure or number. This indicates that NOVP therapy may increase the risks for paternal transmission of chromosomal structural aberrations for sperm produced 32 to 45 days after a treatment with these drugs and implies that there are no excess risks for pregnancies conceived more than 6 months after this therapy. This clinical evaluation of the AM8 sperm FISH protocol indicates that it is a promising tool for assessing an individual's burden of sperm carrying chromosomal structural aberrations as well as aneuploidies after cancer therapy, with broad applications in other clinical and environmental situations that may pose aneugenic or clastogenic risks to human spermatogenesis., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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34. Gonad dose assessment in paediatric kidney nuclear medicine test using Monte Carlo simulation.
- Author
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Lee DY, Kye YU, Kim HJ, Kim JK, and Kang YR
- Subjects
- Child, Computer Simulation, Female, Humans, Kidney Function Tests, Kinetics, Male, Monte Carlo Method, Kidney radiation effects, Nuclear Medicine methods, Ovary radiation effects, Radiation Dosage, Radiometry methods, Testis radiation effects
- Abstract
In this study, we evaluated the effect of radiation dose on gonads during paediatric kidney nuclear medicine tests. Using Monte Carlo simulations, the distribution and effects of radiation were physically evaluated by displaying the distribution path of the source in the human body over time. In particular, the evaluation of doses in children, who are sensitive to radiation during nuclear medicine tests that use internal exposure among several types of medical exposures, was conducted to obtain data for the management of medical exposures. Our results indicated that under normal kidney function, the dose received by the target kidney was 0.430 mGy/mCi, which is ~6% higher than the dose suggested by the International Commission on Radiation Protection (ICRP). Furthermore, when kidney function was compromised, the dose estimated was 0.726 mGy/mCi, which is ~2% lower than the dose suggested by the ICRP. In the male and female gonads, namely the testicles and ovaries, the doses received were 0.359 mGy/mCi and 0.394 mGy/mCi, respectively, under normal kidney function. Similarly, under abnormal kidney function, the doses ranged from 0.187 to 0.353 mGy/mCi and 0.238 to 0.388 mGy/mCi in the male and female gonads, respectively., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)
- Published
- 2020
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35. Lower abdominal and pelvic radiation and testicular germ cell tumor risk.
- Author
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Nead KT, Mitra N, Weathers B, Pyle L, Emechebe N, Pucci DA, Jacobs LA, Vaughn DJ, Nathanson KL, and Kanetsky PA
- Subjects
- Adolescent, Adult, Age Factors, Case-Control Studies, Child, Child, Preschool, Cryptorchidism etiology, Humans, Infant, Infant, Newborn, Logistic Models, Male, Middle Aged, Radiation, Risk Factors, Testis radiation effects, Young Adult, Abdominal Cavity radiation effects, Diagnostic Imaging adverse effects, Neoplasms, Germ Cell and Embryonal etiology, Pelvis radiation effects, Radiation Injuries etiology, Testicular Neoplasms etiology
- Abstract
Background: Testicular germ cell tumor (TGCT) incidence has increased in recent decades along with the use and dose of diagnostic radiation. Here we examine the association between reported exposure to diagnostic radiation and TGCT risk., Methods: We conducted a case-control study of men with and without TGCT recruited from hospital- and population-based settings. Participants reported on exposures to 1) x-ray or CT below the waist and 2) lower GI series or barium enema, which consists of a series of x-rays of the colon. We also derived a combined measure of exposure. We used logistic regression to determine the risk of developing TGCT according to categories of exposures (0, 1-2, or ≥3 exposures) and age at first exposure, adjusting for age, year of birth, race, county, body mass index at diagnosis, family history of TGCT, and personal history of cryptorchidism., Results: There were 315 men with TGCT and 931 men without TGCT in our study. Compared to no exposures, risk of TGCT was significantly elevated among those reporting at least three exposures to x-ray or CT (OR≥3 exposures, 1.78; 95% CI, 1.15-2.76; p = 0.010), lower GI series or barium enema (OR≥3 exposures, 4.58; 95% CI, 2.39-8.76; p<0.001), and the combined exposure variable (OR≥3 exposures, 1.59; 95% CI, 1.05-2.42; p = 0.029). The risk of TGCT was elevated for those exposed to diagnostic radiation at age 0-10 years, compared to those first exposed at age 18 years or later, although this association did not reach statistical significance (OR, 2.00; 95% CI, 0.91-4.42; p = 0.086)., Conclusions: Exposure to diagnostic radiation below the waist may increase TGCT risk. If these results are validated, efforts to reduce diagnostic radiation doses to the testes should be prioritized., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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36. Gamma-irradiation-induced testicular oxidative stress and apoptosis: Mitigation by l-carnitine.
- Author
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Soliman MM, Elshazly SA, and Aldhahrani A
- Subjects
- Animals, Apoptosis drug effects, Biomarkers blood, Male, Mice, Oxidative Stress drug effects, Testis drug effects, Testis metabolism, Testis pathology, bcl-2-Associated X Protein metabolism, bcl-X Protein metabolism, Apoptosis radiation effects, Carnitine pharmacology, Gamma Rays, Oxidative Stress radiation effects, Testis radiation effects
- Abstract
The current study evaluated the potential ameliorative and protective impacts of l-carnitine (L-CAR) against γ-irradiation (RAD)-induced oxidative stress and apoptosis in mice testes. Male Swiss mice were allocated into four groups (n = 7). Group 1 served as a control that received saline intraperitoneally (IP). Group 2 received L-CAR (10 mg/kg bw/day; IP in saline) for 17 days. Group 3 received saline for 17 days and on day 7 exposed to RAD at a dose of 0.1 Gy per day for consecutive 10 days. Group 4 (L-CAR + RAD), received L-CAR same as in group 2 and on day 7 exposed to RAD for consecutive 10 days. Testicular antioxidants (malondialdehyde, MDA; γ-glutamyl-cysteine synthetase, gGCS; and catalase) were altered by γ-irradiation. Preadministration of L-CAR protected γ-irradiated mice from altered changes induced by γ-irradiation. γ-Irradiation affected the mRNA expression of pro-apoptotic, apoptotic, and anti-apoptotic genes (c-jun, c-fos, Bcl-xl, caspase-3, and BAX). All altered genes were ameliorated by prior l-carnitine administration to γ-irradiated mice. Testicular cells showed deformities and edema with congestion in seminiferous tubules and strong immunoreactivity for caspase-9 and a decrease in immunoreactivity of Bcl-2 in histological and immunohistochemical examination. Prior administration of L-CAR to γ-irradiated mice protected this group from reported changes in caspase-9 and Bcl-2 immunostaining. In conclusion, the current study provides evidence for the protective and ameliorative impacts of L-CAR against γ-irradiation-induced testicular oxidative stress and apoptosis at biochemical, molecular, and cellular levels., (© 2020 Wiley Periodicals LLC.)
- Published
- 2020
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37. Restoration of functional sperm production in irradiated pubertal rhesus monkeys by spermatogonial stem cell transplantation.
- Author
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Shetty G, Mitchell JM, Meyer JM, Wu Z, Lam TNA, Phan TT, Zhang J, Hill L, Tailor RC, Peters KA, Penedo MC, Hanna C, Orwig KE, and Meistrich ML
- Subjects
- Animals, Macaca mulatta, Male, Radiation Injuries, Experimental, Adult Germline Stem Cells transplantation, Spermatogenesis physiology, Spermatogonia transplantation, Stem Cell Transplantation methods, Testis radiation effects
- Abstract
Background: In male pre-pubertal cancer patients, radiation and chemotherapy impact future fertility by eradication of spermatogonial stem cells (SSCs). In macaques, spermatogenesis could be regenerated by intratesticular transplantation of SSCs, but only a small percentage of spermatozoa produced were of donor origin. Transient hormone suppression with a GnRH antagonist (GnRH-ant) enhanced spermatogenic recovery from transplanted SSCs., Objectives: To evaluate donor-derived and endogenous spermatogenic recovery after SSC transplantation into irradiated monkeys and to test whether hormone suppression around the time of transplantation facilitates spermatogenic recovery., Materials and Methods: Testes of 15 adult rhesus monkeys were irradiated with 7 Gy and 4 months later transplanted, to one of the testes, with cryopreserved testicular cells containing SSCs from unrelated monkeys. Monkeys were either treated with GnRH-ant for 8 weeks before transplantation, GnRH-ant from 4 weeks before to 4 weeks after transplantation, or with no GnRH-ant. Tissues were harvested 10 months after transplantation., Results: Two of the 15 monkeys, a control and a pre-transplantation GnRH-ant-treated, showed substantially higher levels of testicular spermatogenesis and epididymal sperm output in the transplanted side as compared to the untransplanted. Over 84% of epididymal spermatozoa on the transplanted side had the donor genotype and were capable of fertilizing eggs after intracytoplasmic sperm injection forming morulae of the donor paternal origin. Low levels of donor spermatozoa (~1%) were also identified in the epididymis of three additional monkeys. Transplantation also appeared to enhance endogenous spermatogenesis., Discussion and Conclusion: We confirmed that SSC transplantation can be used for restoration of fertility in male cancer survivors exposed to irradiation as a therapeutic agent. The success rate of this procedure, however, is low. The success of filling the tubules with the cell suspension, but not the GnRH-ant treatment, was related to the level of colonization by transplanted cells., (© 2020 American Society of Andrology and European Academy of Andrology.)
- Published
- 2020
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38. Alpha-lipoic acid effectively attenuates ionizing radiation-mediated testicular dysfunction in rats: Crosstalk of NF-ĸB, TGF-β, and PPAR-ϒ pathways.
- Author
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Said RS, Mohamed HA, and Kassem DH
- Subjects
- Animals, Antioxidants pharmacology, Cytokines biosynthesis, Epithelium drug effects, Epithelium radiation effects, Male, NF-kappa B drug effects, NF-kappa B radiation effects, PPAR gamma drug effects, PPAR gamma radiation effects, Radiation Injuries, Experimental pathology, Rats, Rats, Sprague-Dawley, Spermatozoa drug effects, Spermatozoa radiation effects, Testicular Diseases pathology, Testis pathology, Testis radiation effects, Testosterone blood, Transforming Growth Factor beta drug effects, Transforming Growth Factor beta radiation effects, Whole-Body Irradiation, Gamma Rays, Radiation Injuries, Experimental prevention & control, Radiation-Protective Agents pharmacology, Signal Transduction drug effects, Signal Transduction radiation effects, Testicular Diseases prevention & control, Thioctic Acid pharmacology
- Abstract
Radiotherapy is one of the principal approaches employed in the treatment of pelvic cancers. Nevertheless, testicular dysfunction and infertility are among the most common adverse effects in young adult cancer survivors. Clinically, alpha-lipoic acid (LA) has been applied to improve the quality of sperm with a satisfactory effect. Therefore, the present study investigated the underlying mechanisms of the radioprotective effects of LA against testicular damage. Male Sprague-Dawley rats were exposed to 10 Gy of whole-body ϒ-radiation and LA (50 mg/kg, P.O.) was administered one week before and three days post-irradiation. LA showed remarkable capacity in preserving testicular tissue against radiation damage by improving histological and ultrastructural changes of disorganized seminiferous tubules, besides enhancing its diameter, germinal epithelial thickness, and Johnsen's score. Radiation instigated a significant decrease in sperm quality and quantity associated with depletion of serum testosterone levels, while the LA administration maintained spermatogenesis. Strikingly, LA exhibited antioxidant properties by restoring reduced glutathione levels and antioxidant enzyme activities such as catalase and glutathione-s-transferase, besides diminishing malondialdehyde levels in the testis of irradiated group. Furthermore, LA alleviated testicular inflammation through downregulation of nuclear factor-ĸB (NF-ĸB) expression with a subsequent reduction in interleukin (IL)-6 and cyclooxygenase-2 expression, accompanied by the augmented expression of the anti-inflammatory cytokine IL-10. Additionally, testicular fibrosis markers including Masson's trichrome and transforming growth factor (TGF)-β expression were noticeably declined in LA-treated irradiated rats, together with the upregulation of peroxisome proliferator-activated receptor-ϒ expression. Collectively, LA ameliorates radiation-mediated spermatogenesis-defects and testicular-damage via suppression of oxidative stress/NF-ĸB/TGF-β signaling., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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39. Incidental testicular doses during volumetric-modulated arc radiotherapy in prostate cancer patients.
- Author
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Onal C, Bozca R, Dolek Y, Guler OC, and Arslan G
- Subjects
- Adult, Humans, Lymphatic Metastasis radiotherapy, Male, Phantoms, Imaging, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Organs at Risk radiation effects, Prostatic Neoplasms radiotherapy, Radiotherapy, Intensity-Modulated, Testis radiation effects
- Abstract
Purpose: To compare the incidental testicular doses during volumetric-modulated arc therapy (VMAT) in patients receiving prostate-only and pelvic lymphatic irradiation., Materials and Methods: Testicular doses in 40 intermediate- and high-risk prostate cancer patients were determined on treatment planning system (TPS) using the VMAT technique at 6 MV. Scattered testicular doses were also measured by MOSFET detectors placed on testis surface. The testicular doses of patients treated with prostate-only and pelvic field irradiation were compared., Results: The median testicular doses measured per 200 cGy fraction by TPS and MOSFET detectors were 1.7 cGy (0.7-4.1 cGy) and 4.8 cGy (3.6-8.8 cGy), respectively. The TPS doses and MOSFET readings showed a significant strong correlation (Pearson r = 0.848, p < 0.001). The testicular doses measured by TPS (1.34 ± 0.36 cGy vs. 2.60 ± 0.95 cGy; p < 0.001) and MOSFET (4.52 ± 0.64 cGy vs. 6.56 ± 1.23 cGy; p < 0.001) were significantly lower in patients with prostate-only irradiation than in those with pelvic field irradiation. The mean cumulative scattered dose for prostate-only field delivering 78 Gy was 1.8 Gy and that for pelvic field irradiation was 2.6 Gy, consistent with the reported findings., Conclusions: The patients with prostate-only irradiation received lower testicular doses than those with additional pelvic field irradiation possibly due to the increased scattered doses in large field irradiation using the VMAT technique. The clinical response to increased incidental testicular doses due to pelvic field irradiation remains unknown, and it warrants further investigation.
- Published
- 2020
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40. Low-Dose Radiation Exposure with 56 MnO 2 Powder Changes Gene Expressions in the Testes and the Prostate in Rats.
- Author
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Fujimoto N, Amantayeva G, Chaizhunussova N, Shabdarbayeva D, Abishev Z, Ruslanova B, Zhunussov Y, Azhimkhanov A, Zhumadilov K, Petukhov A, Stepanenko V, and Hoshi M
- Subjects
- Animals, Gamma Rays adverse effects, Male, Nuclear Weapons, Prostate metabolism, Radiation Dosage, Rats, Wistar, Testis metabolism, Gene Expression Regulation radiation effects, Manganese Compounds adverse effects, Oxides adverse effects, Prostate radiation effects, Radiation Exposure adverse effects, Soil Pollutants, Radioactive adverse effects, Testis radiation effects
- Abstract
To investigate the biological effects of internal exposure of radioactive
56 MnO2 powder, the major radioisotope dust in the soil after atomic bomb explosions, on male reproductive function, the gene expression of the testes and the prostate was examined. Ten-week-old male Wistar rats were exposed to three doses of radioactive56 MnO2 powder (41-100 mGy in whole body doses), stable MnO2 powder, or external60 Co γ-rays (2 Gy). Animals were necropsied on Days 3 and 61 postexposure. The mRNA expressions of testicular marker protein genes and prostatic secretory protein genes were quantified by Q-RT-PCR. On Day 3 postexposure, the testicular gene expressions of steroidogenesis-related enzymes, Cyp17a1 and Hsd3b1, decreased in56 MnO2 -exposed groups. Germ cell-specific Spag4 and Zpbp mRNA levels were also reduced. On postexposure Day 61, the Cyp11a1 gene expression became significantly reduced in the testes in the group exposed to the highest dose of56 MnO2 , while another steroidogenesis-related StAR gene mRNA level reduced in the60 Co γ-rays group. There were no differences in Spag4 and Zpbp mRNA levels among groups on Day 61. No histopathological changes were observed in the testes in any group following exposure. Expression in the prostatic protein genes, including CRP1, KS3, and PSP94, significantly decreased in56 MnO2 -exposed groups as well as in the60 Co γ-rays group on Day 61 postexposure. These data suggest that the internal exposure to56 MnO2 powder, at doses of less than 100 mGy, affected the gene expressions in the testis and the prostate, while 2 Gy of external γ-irradiation was less effective.- Published
- 2020
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41. Analysis of testis metabolome and transcriptome from the oriental river prawn (Macrobrachium nipponense) in response to different temperatures and illumination times.
- Author
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Jin S, Hu Y, Fu H, Sun S, Jiang S, Xiong Y, Qiao H, Zhang W, Gong Y, and Wu Y
- Subjects
- Animals, Arthropod Proteins genetics, Male, Palaemonidae, Sex Differentiation, Testis radiation effects, Arthropod Proteins metabolism, Lighting methods, Metabolome, Temperature, Testis metabolism, Transcriptome
- Abstract
A better understanding of the mechanisms underlying the male sexual differentiation of Macrobrachium nipponense is urgently needed in order to maintain sustainable development of the M. nipponense industry. Environmental factors, especially temperature and illumination, have dramatic effects on gonadal development. The aim of the present study was to identify key genes and metabolites involved in the male sexual differentiation and development of M. nipponense through integrated metabolomics and transcriptome analyses of the testis in response to different temperatures and illumination times. A total of 268 differentially abundant metabolites and 11,832 differentially expressed genes (DEGs) were identified. According to integrated metabolomics and transcriptome analyses, glycerophospholipid and sphingolipid metabolism was predicted to have dramatic effects on the male sexual differentiation and development of M. nipponense. According to the KEGG enrichment analysis of DEGs, oxidative phosphorylation, glycolysis/gluconeogenesis, the HIF-1 signaling pathway, the citrate cycle, steroid hormone synthesis, and the spliceosome complex were predicted to promote male differentiation and development by providing adenosine triphosphate, promoting the synthesis of steroid hormones, and providing correct gene products. Quantitative polymerase chain reaction analysis and in situ hybridization showed that the SDHB, PDE1, HSDL1, CYP81F2, SRSF, and SNRNP40 genes were differentially expressed, suggesting roles in the male sexual differentiation and development of M. nipponense. Strong candidate sex-related metabolic pathways and genes in M. nipponense were identified by integrated metabolomics and transcriptome analyses of the testis in response to different temperatures and illumination times, as confirmed by PCR analysis and in situ hybridization., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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42. Simple variance reduction in Monte Carlo calculations of specific absorbed fractions: Russian roulette and splitting at the source organ.
- Author
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Díaz Londoño G, García-Pareja S, Salvat F, and Lallena AM
- Subjects
- Algorithms, Anthropometry, Computer Simulation, Computers, Female, Humans, Male, Models, Theoretical, Ovary radiation effects, Phantoms, Imaging, Photons, Radiation Dosage, Radiometry methods, Reference Values, Testis radiation effects, Urinary Bladder radiation effects, Uterus radiation effects, Monte Carlo Method, Radiometry instrumentation, Signal Processing, Computer-Assisted, Thyroid Gland radiation effects
- Abstract
Purpose: To investigate the capabilities of several variance reduction techniques in the calculation of specific absorbed fractions in cases where the source and the target organs are far away and/or the target organs have a small volume., Methods: The specific absorbed fractions have been calculated by using the Monte Carlo code PENELOPE and by assuming the thyroid gland as the source organ and the testicles, the urinary bladder, the uterus, and the ovaries as the target ones. A mathematical anthropomorphic phantom, similar to the MIRD-type phantoms, has been considered. Photons with initial energies of 50, 100 and 500 keV were emitted isotropically from the volume of the source organ. Simulations have been carried out by implementing the variance reduction techniques of splitting and Russian roulette at the source organ only and the interaction forcing at the target organs. The influence of the implementation details of those techniques have been investigated and optimal parameters have been determined. All simulations were run with a CPU time of 1.5 · 10
5 s., Results: Specific absorbed fractions with relative uncertainties well below 10% have been obtained in most cases, agreeing with those used as reference. The best value for the factor defining the application of the Russian roulette technique was r = 0.3. The best value for the splitting number was between s = 3 and s = 10, depending on the specific energies and target organs., Conclusions: The proposed strategy provides an effective method for computing specific absorbed fractions for the most unfavorable situations, with a computing effort that is considerably reduced with respect to other methodologies.- Published
- 2020
- Full Text
- View/download PDF
43. Pelvic Radiation-Induced Testicular Damage: An Experimental Study at 1 Gray.
- Author
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Rakici SY, Guzel AI, Tumkaya L, Sevim Nalkiran H, and Mercantepe T
- Subjects
- Animals, Apoptosis radiation effects, Caspase 3 metabolism, DNA chemistry, DNA radiation effects, Female, Genes, X-Linked radiation effects, Germ Cells, In Situ Nick-End Labeling, Male, Pregnancy, Radiation Dosage, Rats, Sex Ratio, Gamma Rays, Pelvis radiation effects, Radiation Injuries, Experimental pathology, Testis pathology, Testis radiation effects
- Abstract
Therapeutic radiation of the pelvic region has been shown to cause damage to testicular germ cells. In this study we aimed to evaluate the effects of a low therapeutic dose of 1 Gy on the induction of cellular and histological damage in early-stage testicular germ cells and the impact of this radiation on offspring sex ratio. Unirradiated and irradiated male rats were mated with unirradiated female rats. Female rats were followed and the sex of the offspring was determined. The male rats were sacrificed at the end of the second week, and the testicular germ cells were subjected to genetic analysis along with cytological and histopathological examination. Sperm DNA was amplified with primers specific to testis-specific Y-linked protein, rat actin beta and testis-specific X-linked genes. The resulting products were separated by capillary electrophoresis. Histopathological changes were investigated by light microscopy along with the TUNEL assay and immunohistochemical staining for caspase-3. There was no significant difference between the two groups for sex ratio and size of offspring. The number of sperm cells bearing X or Y chromosomes' did not differ significantly between these two groups. However, a 1 Gy dose of radiation caused significant cytopathological and histopathological changes in the testicular tissue. In the irradiated group, edematous regions were evident. The number of caspase-3 positive cells in the germinal epithelium of the seminiferous tubules was also significantly higher in the irradiated group. Our results showed that low-dose radiation induced apoptosis and caused significant cyto- and histopathological changes in the testicular tissue. Further research is required to fully elucidate their contribution to apoptosis and if low-dose radiation may potentially lead to long-term effects in the offspring. These results may also lead us to develop a new technique using the caspase-3 staining to monitor the susceptibility to low dose radiation.
- Published
- 2020
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44. Monophosphoryl lipid A alleviated radiation-induced testicular injury through TLR4-dependent exosomes.
- Author
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Liu Z, Cao K, Liao Z, Chen Y, Lei X, Wei Q, Liu C, Sun X, Yang Y, Cai J, and Gao F
- Subjects
- Abnormalities, Radiation-Induced drug therapy, Abnormalities, Radiation-Induced pathology, Animals, Disease Models, Animal, Exosomes drug effects, Humans, Lipid A chemistry, Lipid A genetics, Lipid A pharmacology, Male, Mice, Radiation Protection, Testis drug effects, Testis pathology, Testis radiation effects, Toll-Like Receptor 4 agonists, Abnormalities, Radiation-Induced genetics, Lipid A analogs & derivatives, Testis injuries, Toll-Like Receptor 4 genetics
- Abstract
Radiation protection on male testis is an important task for ionizing radiation-related workers or people who receive radiotherapy for tumours near the testicle. In recent years, Toll-like receptors (TLRs), especially TLR4, have been widely studied as a radiation protection target. In this study, we detected that a low-toxicity TLR4 agonist monophosphoryl lipid A (MPLA) produced obvious radiation protection effects on mice testis. We found that MPLA effectively alleviated testis structure damage and cell apoptosis induced by ionizing radiation (IR). However, as the expression abundance differs a lot in distinct cells and tissues, MPLA seemed not to directly activate TLR4 singling pathway in mice testis. Here, we demonstrated a brand new mechanism for MPLA producing radiation protection effects on testis. We observed a significant activation of TLR4 pathway in macrophages after MPLA stimulation and identified significant changes in macrophage-derived exosomes protein expression. We proved that after MPLA treatment, macrophage-derived exosomes played an important role in testis radiation protection, and specially, G-CSF and MIP-2 in exosomes are the core molecules in this protection effect., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
- Published
- 2020
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45. Safety parameters of in vivo low-energy shock waves and their impact on adult rat testes.
- Author
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Xing J, Yu G, Li D, Tan S, Cao H, Liu Z, and Bai Z
- Subjects
- Animals, Male, Oxidative Stress, Rats, Semen Analysis, Spermatozoa radiation effects, Testis anatomy & histology, Testis chemistry, Testis ultrastructure, Testis radiation effects
- Abstract
Low-energy shock waves (LESWs) have been widely used in the intervention of a subset of diseased tissues and organs with good results. However, it is unclear whether they can be used directly to intervene in the testes. Therefore, the aim of this study was to determine a relatively safe energy density and impulse number for rat testes. A total of 176 male rats were randomly and equally assigned to different intervention groups. Among them, 144 rats were assigned to 18 shock subgroups with different energy densities (0.02, 0.04 and 0.06 mJ/mm
2 ), different impulse numbers (500, 1000 and 1500 impulses) and different shock periods (2 and 8 weeks). The remaining 32 rats were divided into the sham intervention (S) groups and the blank control (N) groups with observation periods of 2 weeks and 8 weeks. One day after the last LESWs intervention, all the rats were weighed, and the concentrations of reproductive endocrine hormones were measured, the semen quality and testicular tissue oxidative stress levels were analyzed, and histomorphology and ultrastructures were observed. We found that there were no significant differences in the whole-body physiological state, testicular tissue morphology, oxidative stress state and sperm quality between the L1 shock group and the corresponding S group and N group (all p˃0.05, respectively). However, the other parameters of the shock groups caused different degrees of damage to the structure and function of rat testes, and the whole-body physiological state was also adversely affected. This study demonstrated that LESWs with an energy density of 0.02 mJ/mm2 and 500 impulses had no adverse effects on the rat testes., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2020
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46. A Chinese herbal prescription Yiqi Jiedu decoction attenuates irradiation induced testis injury in mice.
- Author
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Wang A, Wang L, Lu X, Wang Y, Chen X, Shi Z, Li P, He C, Zhang S, Gao Y, Wang T, and Hu S
- Subjects
- Animals, Apoptosis drug effects, Apoptosis radiation effects, Interleukin-6 metabolism, Male, Mice, Inbred BALB C, Myeloid Differentiation Factor 88 metabolism, NF-kappa B metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Spermatogenesis drug effects, Spermatogenesis radiation effects, Testis pathology, Toll-Like Receptor 5 metabolism, Tumor Necrosis Factor-alpha metabolism, Whole-Body Irradiation, Drugs, Chinese Herbal pharmacology, Gamma Rays, Testis injuries, Testis radiation effects
- Abstract
Objective: Yiqi Jiedu (YQJD) decoction is a Chinese herbal prescription, based on an experienced expert of traditional Chinese medicine. It is used for the injuries caused by radiotherapy. The current study was designed to investigate the protective effects of YQJD decoction on radiation damage of testis in mice, and to explore its potential mechanisms., Methods: Mice were randomly divided into blank control group (Ctrl), model group (IR), positive drug group (IRA), and YQJD decoction group (IRY). After 10-day period intervention, they were whole-body irradiated with 2 Gy
60 Co γ-rays and sacrificed on 7th day after irradiation. The indicators including the index and histopathology examination of testis, spermatogenic cell types and apoptosis, and the expression of TLR5, MyD88, NF-κB, TNF-α, IL-6 and Bcl-2 in testis., Results: The testis atrophied significantly on 7th day of exposure to radiation, while YQJD decoction promoted the recovery of testis index and structure. Moreover, spermatogenic cell types and apoptosis had significant changes after irradiation. YQJD decoction protected the testicular function of spermatogenesis, as while as reduced the apoptosis rate of spermatogenic cells. In addition, RT-PCR and immunohistochemical analysis showed that YQJD decoction up-regulated the expression of TLR5 in testis. The levels of TLR5's downstream factors were also up-regulated in YQJD decoction group, which indicated that TLR5 signaling pathway might play an important role in the protective effects of YQJD decoction., Conclusions: The results showed that YQJD decoction attenuated irradiation induced testis injury in mice. Its potential mechanism was related to TLR5 signaling pathway., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)- Published
- 2020
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47. In vitro study of effects of ELF-EMF on testicular tissues of roe deer (Capreolus capreolus) - FTIR and FT-Raman spectroscopic investigation.
- Author
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Koziorowska A, Depciuch J, Kozioł K, Nowak S, and Lach K
- Subjects
- Animals, Male, Testis chemistry, Time Factors, Deer, Electromagnetic Fields adverse effects, Spectroscopy, Fourier Transform Infrared, Spectrum Analysis, Raman, Testis radiation effects
- Abstract
Electromagnetic fields (EMF) are classified as an environmental factor affecting living organisms. The aim of the study was to evaluate the effect of EMF at different frequencies (50 and 120 Hz), durations of treatment (2 and 4 h) and with the magnetic induction of 8 m T on testicular tissues of roe deer (Capreolus capreolus) in vitro by comparison with the control samples. Fourier Transform Raman Spectroscopy (FT-Raman) and Fourier Transform Infrared Spectroscopy (FTIR) were utilized in this study to identify the chemical changes in the testicular tissues. The FTIR and FT-Raman spectroscopy methods were used to evaluate differences in spectra of the treated tissues compared to the control group. The results from the analysis of the spectra indicated there were characteristic differences in the testicular tissue compared with the control samples. There was identification of peaks attributed to different biochemical components. Comparing the spectra for different frequencies and treatment times, there was a greater intensity of peaks originating from most of the functional groups in the tissues evaluated. With the FTIR spectra, there were five of 15 peaks, while with the FT-Raman spectra, there were six of ten peaks that were shifted. For FTIR and FT-Raman analyzed spectral ranges, results from the PCA analysis indicate there was no similarity between control groups (2 and 4 h) and samples treated with EMF at a frequency of 120 Hz for 2 and 4 h. In conclusion, therefore, EMF is an environmental factor affecting the testis of roe deer., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
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48. The potential effect of methylseleninic acid (MSA) against γ-irradiation induced testicular damage in rats: Impact on JAK/STAT pathway.
- Author
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Gawish RA, Fahmy HA, Abd El Fattah AI, and Nada AS
- Subjects
- Animals, Antioxidants metabolism, Glutathione metabolism, Interleukin-1beta metabolism, Male, NF-E2-Related Factor 2 metabolism, NF-kappa B metabolism, Oxidative Stress drug effects, Oxidative Stress radiation effects, Rats, Rats, Sprague-Dawley, Sperm Head drug effects, Sperm Head pathology, Sperm Head radiation effects, Superoxide Dismutase metabolism, Suppressor of Cytokine Signaling 3 Protein metabolism, Testis cytology, Testis metabolism, Janus Kinases metabolism, Organoselenium Compounds pharmacology, Radiation-Protective Agents pharmacology, STAT Transcription Factors metabolism, Testis drug effects, Testis radiation effects
- Abstract
This study suggested that methylseleninic acid (MSA) could respond to the inflammatory signaling associated with ionizing radiation-induced testicular damage. Mature male rats were divided into four groups: negative control, whole body γ-irradiated (IRR) (5 Gy), MSA (0.5 mg/kg, daily for nine consecutive days), and MSA+ IRR groups. MSA increased serum testosterone level and testicular glutathione peroxidase (GPx) as well as decreased the percentage of sperm abnormalities. Radiation prompted inflammatory signaling in the testes through increasing phospho-janus kinase1 (p-JAK1), phospho-signal transducers and activators of transcription 3 (p-STAT3) protein expressions. This induced increment in the inflammatory markers including nuclear factor- kappa B (NF-κB) and interleukin-1beta (IL-1β) levels. Also, radiation induced elevation of nitric oxide (NO) and malondialdhyde (MDA) levels with consequent reduction in testicular reduced glutathione level (GSH) and superoxide dismutase (SOD) activity. MSA significantly counteracted the radiation effect on testicular nuclear factor erythroid-2-related factor-2 (Nrf2) and suppressor of cytokine signaling (Socs3) protein expressions. In summary, this investigation proposed that MSA preserved spermatogenesis through increasing testosterone levels and GPx activity. Additionally, it diminished testicular inflammation by increasing of Nrf2 and Socs3 levels leading to reducing of p-JAK1, p-STAT3 and NF-κB levels. Histopathological examination results of testicular tissues showed a coincidence with the biochemical analysis., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2020
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49. Phytochemical profile and protective effect of Ocimum basilicum aqueous extract in doxorubicin/irradiation-induced testicular injury.
- Author
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Ibrahim RYM, Mansour SM, and Elkady WM
- Subjects
- Animals, Apoptosis radiation effects, Apoptosis Regulatory Proteins metabolism, Cell Proliferation radiation effects, Male, NF-kappa B metabolism, Oxidative Stress radiation effects, Phytochemicals isolation & purification, Plant Extracts isolation & purification, Protective Agents isolation & purification, Rats, Wistar, Signal Transduction, Testis metabolism, Testis pathology, Testis radiation effects, Antibiotics, Antineoplastic toxicity, Apoptosis drug effects, Cell Proliferation drug effects, Doxorubicin toxicity, Ocimum basilicum chemistry, Oxidative Stress drug effects, Phytochemicals pharmacology, Plant Extracts pharmacology, Protective Agents pharmacology, Testis drug effects
- Abstract
Objectives: Combined chemotherapy and radiotherapy usually associated with various comorbidities especially on rapidly proliferating cells as testis. This study aimed to characterize main constituents of Ocimum basilicum L. (OB) aqueous extract and examine its protective effect on doxorubicin/irradiation (DOXO/IR)-induced testicular injury in rats., Methods: Spectrophotometric analysis showed considerable amount of polyphenolic (146.31 µg/mg) and flavonoid contents (28.63 µg/mg); UPLC-ESI-MS/MS analysis revealed that the major flavonoid was apigenin-O-glucoside (7.53%) followed by luteolin (5.94%), while rosmarinic acid was the major polyphenolic (15.76%) followed by caftaric acid (9.39%); rutin and querctin were also present and were quantified using high-performance liquid chromatography. Administration of OB extract (200 mg/kg per day; p.o.) to DOXO/IR rats resulted in marked improvement of associated testicular damage., Key Findings: Ocimum basilicum L. significantly decreased testicular levels of nuclear factor-kappa B and B-cell lymphoma-2 (Bcl2)-associated protein X, along with caspase-3 immunohistochemical staining. In addition, OB elevated testicular total antioxidant capacity, nuclear erythroid-related factor-2, Bcl2 and testosterone contents and Ki-67 immunohistochemical staining. Such changes were also accompanied by restoration of testicular architecture., Conclusions: The study highlights the protective role of OB aqueous extract in hampering most of the harmful chemotherapy/radiotherapy-induced outcomes via its antioxidant, antiapoptotic and cell regeneration abilities. Such findings may offer an incentive in expanding its use during chemotherapy and radiotherapy., (© 2019 Royal Pharmaceutical Society.)
- Published
- 2020
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50. Long-term exposure to 4G smartphone radiofrequency electromagnetic radiation diminished male reproductive potential by directly disrupting Spock3-MMP2-BTB axis in the testes of adult rats.
- Author
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Yu G, Tang Z, Chen H, Chen Z, Wang L, Cao H, Wang G, Xing J, Shen H, Cheng Q, Li D, Wang G, Xiang Y, Guan Y, Zhu Y, Liu Z, and Bai Z
- Subjects
- Animals, Male, Radio Waves, Rats, Reproduction, Electromagnetic Radiation, Smartphone, Testis radiation effects
- Abstract
The correlation between long-term exposure to SRF-EMR and the decline in male fertility is gradually receiving increasing attention from the medical society. While male reproductive organs are often exposed to SRF-EMR, little is currently known about the direct effects of long-term SRF-EMR exposure on the testes and its involvement in the suppression of male reproductive potential. The present study was designed to investigate this issue by using 4G SRF-EMR in rats. A unique exposure model using a 4G smartphone achieved localized exposure to the scrotum of the rats for 6 h each day (the smartphone was kept on active talk mode and received an external call for 1 min over 10 min intervals). Results showed that SRF-EMR exposure for 150 days decreased sperm quality and pup weight, accompanied by testicular injury. However, these adverse effects were not evident in rats exposed to SRF-EMR for 50 days or 100 days. Sequencing analysis and western blotting suggested Spock3 overexpression in the testes of rats exposed to SRF-EMR for 150 days. Inhibition of Spock3 overexpression improved sperm quality decline and alleviated testicular injury and BTB disorder in the exposed rats. Additionally, SRF-EMR exposure suppressed MMP2 activity, while increasing the activity of the MMP14-Spock3 complexes and decreasing MMP14-MMP2 complexes; these results were reversed by Spock3 inhibition. Thus, long-term exposure to 4G SRF-EMR diminished male fertility by directly disrupting the Spock3-MMP2-BTB axis in the testes of adult rats. To our knowledge, this is the first study to show direct toxicity of SRF-EMR on the testes emerging after long-term exposure., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
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