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SummaryFertility preservation is one of the most important issues in assisted reproductive technology. Previous studies have shown that cytokines and growth factors can improve follicle growth. The endometrial stromal cells secrete various factors that are involved in maintaining the integrity of uterine and epithelial secretory function. The platelet-rich plasma contains a large assembly of platelets suspended in plasma that successfully improves the viability and growth of various cell lines. This work aimed to investigate the influences of conditioned medium (CM) and platelet-rich plasma (PRP) on the development of ovarian follicles in infertile mice due to cyclophosphamide (CYC) exposure. In this study, 65 healthy BALB/c female mice (∼28–30 g and 6-8 weeks old) in five groups were studied. Immunohistochemistry (IHC) was used to detect growth differentiation factor 9 (GDF9)-positive cells. The mRNA expression levels of SMAD1, SMAD2, and BMP15 was assessed using reverse transcription-polymerase chain reaction (RT-PCR) method. The expression levels of SMAD1, GDF9, BMP15, and SMAD2 in the CM+PRP group was significantly more than in the CM and PRP groups. In addition, live birth occurred in the CM+PRP group. Treatment with CM+PRP in infertile mice due to Cy exposure increased fertility and live-birth rate. In general, our study suggested that the CM and PRP combination could improve the growth of mice ovarian follicles in vivo.

SummaryStable ovarian function is a key factor in the performance of the reproductive system. In contrast, some ovarian function-related diseases, such as polycystic ovarian syndrome, premature ovarian failure (POF), and ovarian cancer, are the main cause of infertility and death of women around the world. Despite multiple attempts, there are no effective tools against these conditions; however, mesenchymal stem cell-based therapy, especially using adipose tissue, has attracted much attention in medicine in light of its advantages such as easy isolation and accessibility. Conversely, it has been suggested that MSC-conditioned medium (CM) can restore injured tissues and has high immunocompatibility. So, here, we will summarize the effects of administration of MSCs and CM derived from adipose tissue on ovarian functions and related diseases.

Background: Recent studies have demonstrated that adipose mesenchymal stem cells (AMSCs)-derived secretome (AMSC-Se) has anticancer impacts. Objectives: This study investigated the cytotoxic impacts of AMSC-Se on a colon carcinoma cell (HT-29) line. Methods: The colon cancer cells were exposed to 50 or 100 µg/mL ASMC-Se for 24 hours. MTT test had used to examine the impacts of ASMC-Se on the survival rates of the cells. Caspase activity, mRNA, and protein expression of Bax and Bcl-2 had evaluated to determine apoptosis. Results: ASMC-Se could diminish the survival of the cells concentration-dependently. The mRNA and protein expression of Bax was concentration-dependently elevated, while Bcl-2 expression decreased in the ASMC-Se group compared to the control concentration-dependently (P < 0.05). The caspase-3 and caspase-9 activities were concentration-dependently enhanced (P < 0.05), while the caspase-8 activity did not change with the AMSC-Se. Conclusions: These findings indicate that AMSC-Se effectively prevents cell growth and induces apoptosis by stimulating the intrinsic apoptotic pathway in these cells.

Background: Men’s sexual health is one of the main aspects of their lives. Male sexual dysfunction (SD) includes a wide range of sexual impairments and is not limited to premature ejaculation (PE) and erectile dysfunction (ED). ED can be a life-changing issue that might be mixed up with male sexual impotence characterized by PE and ED. Objectives: The objectives of this study were to estimate the prevalence of sexual dysfunction and its associated factors among the Iranian male population. Methods: This is a cross-sectional study for which data was collected from a nationwide reproductive morbidities project among males in Iran. To do so, 2296 men aged 25 - 60 years were selected from four provinces by cluster sampling. Statistical analysis was done in SPSS (18.0.0) Results: The prevalence of severe/medium SD and severe SD were 66.9% and 18.1%, respectively. The prevalence of low sexual satisfaction, low sexual desire, and dissatisfaction with the length of intercourse before orgasm were 9.5%, 9%, and 12%. Conclusions: Sexual dysfunction is highly likely prevalent among less educated, unemployed men with a history of chronic diseases. Various educational programs to raise awareness are thoroughly recommended.

Autoimmune disease, caused by unwanted immune responses to self-antigens, affects millions of people each year and poses a great social and economic burden to individuals and communities. In the course of autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, and multiple sclerosis, disturbances in the balance between the immune response against harmful agents and tolerance towards self-antigens lead to an immune response against self-tissues. In recent years, various regulatory immune cells have been identified. Disruptions in the quality, quantity, and function of these cells have been implicated in autoimmune disease development. Therefore, targeting or engineering these cells is a promising therapeutic for different autoimmune diseases. Regulatory T cells, regulatory B cells, regulatory dendritic cells, myeloid suppressor cells, and some subsets of innate lymphoid cells are arising as important players among this class of cells. Here, we review the roles of each suppressive cell type in the immune system during homeostasis and in the development of autoimmunity. Moreover, we discuss the current and future therapeutic potential of each one of these cell types for autoimmune diseases.

Some studies have shown that Ritalin can interfere with the growth and development of the reproductive system and can also have a serious and harmful effect on sperm parameters, so we decided to conduct studies in this field on the human sample. In a case-control study, 100 adult men aged 21-31 years with hyperactivity were divided into two groups of 50 past users and 50 current users and, 50 patients who had not used Ritalin before were included as the control group. Data were analysed using SPSS software, version 20. Analysis of variance, Pearson correlation coefficient, and regression analysis was used to assess the correlation between variables. The results also showed that there was a statistically significant difference between the current users and the control group in terms of sperm count, abnormality, and motility (p .47). Comparison of the user group in the past and the control group showed that there was no statistically significant difference in terms of sperm count (p .59), but there was a significant difference in terms of sperm motility and abnormality between the two groups (p .001). The present study showed that long-term use of Ritalin can have negative effects on sperm parameters in humans.

Ovarian cryopreservation is one of the effective methods to preserve fertility for cancer patients. Still, some problems have been expressed with this approach, namely ROS, resulting in adverse effects on oocytes and ovarian follicles. Kisspeptin as an antioxidant control ovarian function, directly or indirectly. In this study, the effect of kisspeptin on follicle maturation was evaluated in culture following ovarian cryopreservation. Ovarian tissue samples of women between 20 and 35 years old (n = 12) were collected laparoscopically. Samples were randomly divided into four groups: 1) control, 2) vitrification, 3) vitrified + 1µM kisspeptin, and 4) vitrified + 10µM kisspeptin. After vitrification and thawing processes, the tissues were cultured in DMEM medium for 7 days. H&E staining for histological evaluation, Real-Time PCR for GDF9 and BMP15 gene expression, and immunohistochemical staining for GDF9 and BMP15 protein expression were performed. In the vitrification group, ovarian tissue morphology was incoherent, and more primordial follicles than other follicle types were found. The expression of GDF9 and BMP15 genes and proteins were significantly decreased in this group compared with other groups (p

Cell encapsulation utilizing biodegradable material has promising outcomes for tissue engineering. From a long time ago, alginate has been generally utilized for drug delivery, cell transplantation and as a scaffold in biomedical applications. The aim of this study was the comparison of cell viability in the presence of two polymerizing ions: Ba2+ and Ca2+ to improvement the quality of alginate scaffold. For this purpose, WJMSCs after three passage were encapsulated in alginate scaffold in the presence of Ba2+ and ca2+. Cell viability was evaluated by WST-8 assay kit after 24, 48 and 72 hours. The results showed that encapsulated cells in the presence of Ca2+ had more viability than Ba2+. It was also found that using the WST-8 assay kit is a convenient and fast method for evaluation the viability of cells. It can be claimed that Calcl2 polymerizing solution provides more favorable conditions for cell viability compared to Bacl2 solution. Running title: Assessing the viability of stem cells by WST-8 assay kit

Breast cancer (BC), as the most common cancer among women, affects a great number of subjects around the world. This heterogenic disease is divided into several types and subtypes, and each subtype has various phenotypes and genotypes. Against BC, several options have been proposed, such as surgery, radiotherapy, and chemotherapeutic agents. However, these approaches may have detrimental effects on health and life quality of patients. Hence, harnessing a therapeutic tool with high effectiveness and low side effects is required. Recently, mesenchymal stem cells (MSCs) have created a new window to treat various disorders, like cancer, and among these, umbilical cord (UC)-derived MSCs have acquired much interest due to their advantages. Therefore, in this narrative review, the influences of UC-derived MSCs on BC were reviewed and summarized with a focus on the molecular mechanisms involved in its pathogenesis and treatment.

Background: Osteoarthritis (OA), as one of the chronic debilitating conditions, affects 15% of people globally and is linked with serious problems, such as cardiovascular diseases, metabolic syndrome, and autoimmune inflammatory disorders. The current therapeutic options for this disease include nonsteroidal anti-inflammatory drugs, surgery, gene therapy, intrasynovial gel injection, and warm needle penetration. However, these approaches may be accompanied by considerable side effects, high costs, and some limitations for patients. Thus, using an alternative way is needed. Summary: Presently, natural compounds based-therapies, like flavonoids, have acquired much attention in the current era. One of the compounds belonging to the flavonoid family is quercetin, and its therapeutic effects on disorders related to joints and cartilage have been addressed in vivo and in vitro studies. Key Messages: In this review, we summarized evidence indicating its curative capacity against OA with a mechanistic insight.

Several factors are necessary for the growth and survival of healthy follicles in the folliculogenesis process, including endocrine and paracrine glands, and a regulated ratio of granulosa cells to oocytes. One of the most powerful methods for studying folliculogenesis is the culture of ovarian follicles and oogenesis within a completely controlled environment. Follicle culture systems are highly developed and are rapidly evolving. However, the methods for separating the follicles, the cultivation techniques, the culture medium, and the dietary and hormonal supplements vary depending on the species studied. This study made a literature review of follicular culture techniques, and we investigated the heterogeneity among these key variables in follicular culture.

Both genomic instability and the presence of chronic inflammation are involved in carcinogenesis and tumor progression. These alterations predispose the cancer cells to undergo metabolic reprogramming as well as the epithelial-mesenchymal transition (EMT). These pathways allow cancer cells to avoid apoptosis and stimulate tumor progression. EMT is an important early event in tumor cell invasion, which can be regulated through inflammatory signaling pathways. Cancer cells undergoing EMT are vulnerable to cell death by the process of ferroptosis. Ferroptosis is a form of regulated cell death involving iron-dependent lipid peroxidation, designed to maintain cellular homeostasis. Several reports have linked ferroptosis, inflammation, and cancer. Ferroptosis inhibitors and EMT inducers have been used to understand the anti-inflammatory and anticancer effects in experimental models. A better understanding of the crosstalk between ferroptosis and EMT, and the involvment of inflammatory mediators may accelerate the discovery of therapeutic strategies to eradicate cancer cells and overcome drug-resistance.

SummaryMale infertility is responsible for 50% of men’s health problems and has always been a concern for personal and social issues. A survey of global statistics suggests an increase in infertility rate as one of the critical issues documented in studies. There are different ways of maintaining fertility in men, depending on their age. In this paper, we review the preservation methods used for fertility treatment in Iran and other countries. Available data were reviewed from Google Scholar, PubMed, Scopus, Web of Science, IranMedex, MEDLIB, IranDoc and Scientific Information Database and searched for articles published up to 2018, using the medical subject heading (MeSH) terms for cryopreservation, sperm, testicular, spermatogonia stem cell, male infertility and/or Iranian and in the world, to provide evidence from evaluation of fertility preservation the methods. Based the search strategy, 274 manuscripts were found. After reviewing the titles, abstracts and manuscripts in their entirety, 119 articles were obtained and selected according to the eligibility criteria. The 85 studies mentioned above were divided into three categories (sperm, testis, and spermatogonia stem cells (SSCs)), and methods of fertility preservation were investigated. Ways to maintain male fertility were different depending on age, and included sperm, testicular, and SSC freezing. The number of studies on testicular tissue and SSCs was low for human samples, and more studies are still needed. Sperm freezing at infertility centres is the top for male fertility preservation.

Background: Sexually transmitted diseases (STDs), especially in men, can lead to multiple morbidities and facilitate the transmission of serious pathogens, such as the human immunodeficiency virus. The present study used the data from a nationwide survey on male morbidities to estimate the prevalence of STDs among men in Iran. Methods: This cross-sectional study used the data from a nationwide project on male reproductive morbidities in 2007. A total of 2296 men within the age range of 25 - 60 years were recruited by systematic cluster sampling from four provinces (i.e., Golestan, Hormozgan, Kermanshah, and Isfahan, Iran). The data on the symptoms of STDs, including genital secretion, pushing out, itching or genital ulcers, and lymphadenopathy of the inguinal area after sexual contact, were collected by trained urologists. Data analysis was carried out using SPSS software (version18.0, Chicago, IL, USA). The independent samples t-test and chi-square test were used for data analysis. Results: A total of 2296 men with a mean age value of 39.95 ± 10.3 years were interviewed in this study. Two-thirds of all the subjects (75%) were aware of using condoms in suspected sexual relationships; however, only 69% of the aforementioned subjects used condoms in those circumstances. Overall, 14 subjects (0.6%) had one type of STDs at the study time. Moreover, 110 subjects (4.7%) answered “yes” to the question of whether they were referred to a physician for sexual problems. Conclusions: The prevalence of STDs is still low among the male population in Iran. Careful and well-designed surveillance systems to monitor the incidence of STDs and proper preventive measures to restrict the spread of sexually transmitted pathogens are among the proposed recommendations.

Secreted factors (secretome) of Wharton’s jelly mesenchymal stem cells (WJMSCs) have therapeutic impacts. This study was conducted to investigate the impact of WJMSCs-derived secretome (WJMSCs-Se) in apoptosis and the growth of HT-29 cells. HT-29 cells treated with 25 or 50 μg/mL WJMSCs-Se for 24 h. Colony formation and MTT test was used to assess the proliferation and cytotoxicity of the HT-29 cells. Annexin V/PI staining was done for the assessment of apoptosis. The mRNA expression of important apoptosis-related genes was also examined. In the WJMSCs-Se-treated HT-29 cells, colony numbers and viability percentages were significantly reduced in a concentration-dependent manner. Apoptotic and necrotic indexes of WJMSCs-Se-treated HT-29 cells considerably enhanced in comparison to the control. The Caspase-9 and -3 activities were significantly increased in the WJMSCs-Se-exposed HT-29 cells. The mRNA expression of Caspase-9, Caspase-3, and Bax/ Bcl-2 ratio was considerably elevated in the WJMSCs-Se-treated HT-29 cells. Caspase-8 activity and expression of the p53 gene were not affected by the WJMSCs-Se. Taken together, we concluded that WJSCs-Se significantly prevented cell growth and enhanced colon cancer cell death in a concentration-dependent manner mainly through the intrinsic apoptotic pathway.

Objective: Destruction of pancreatic beta-cells induces an insulin deficiency and causes type 1 diabetes. The role of autophagy in inducing insulin-secreting cells (ISCs) from adipose-derived mesenchymal stem cells (AMSCs) was investigated in the current study. Materials and Methods: In this experimental study, the isolated AMSCs were characterization and exposed to a cocktail differentiation medium (CDM) in the absence or presence of 3-methyladenine (3MA), an autophagy inhibitor. The differentiation of ISCs was confirmed by the evaluation of the expression of beta-cell-specific genes including pancreatic and duodenal homeobox 1 (PDX1), musculoaponeurotic fibrosarcoma oncogene homolog A (MAF-A), Nk class of homeodomain-encoding genes 6.1 and 2.2 (NKX6-1 and NKX2.2), Glucose transporter 2 (GLUT-2) and INSLIN. Using Newport Green (NG), insulin-positive cells were identified. Insulin secretion in response to various glucose concentrations was measured. Autophagy was evaluated by Acridine orange (AO) staining. Also, expression of autophagy-associated genes, including autophagy-related gene 5 (ATG-5), autophagy-related gene 7 (ATG-7), BECLIN-1, and mammalian target of rapamycin (mTOR), was evaluated by Real-time polymerase chain reaction (PCR) method. Results: We observed a significant increase of beta-cell specific genes expression in the CDM-treated cells (P

Previous studies have demonstrated a relationship between gender and COVID-19 outcomes. In addition, this is confirmed that men have more danger of progressing an acute type of the illness than women, specifies the significance of miscellaneous data related to male and female patients with COVID-19. In other words, some factors like hormonal levels and immune function may interact with each other. A perception of the fundamental reasons for gender diversities in COVID-19 patients can beget a chance for disease prevention and faster treatment. The present study evaluates the role of gender in the incidence and progression of the COVID-19 disease. It has been explained that how gender affects angiotensin-converting enzyme 2 (ACE2), which is a basic factor for the COVID-19 pathogenesis introducing the sex diversities in platelet function, immune reactions and how sex hormones affect immune functions, also the effect of androgens on transmembrane protein serine protease 2 (TMPRSS2) receptor in COVID-19 patients was investigated.

Introduction: Previous studies have proven that secretory materials of mesenchymal stem cells (MSCs) (secretome) have remedial properties. Objectives: The main goal of this study was to evaluate the effects of secretome of adipose-derived MSCs on growth and apoptosis in anaplastic thyroid carcinoma (ATC) C-643 cells. Materials and Methods: Initially, thyroid carcinoma cells were exposed to the 25 and 50 μg/mL adipose-derived stem cells (ADSCs) secretome for 24 and 48 hours, to evaluate the proliferation and cytotoxicity of the C-643 cells, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test and colony assay was conducted. Acridine orange/ethidium bromide (AO/EB) staining was conducted to evaluate the apoptosis. The expression level of apoptosis-associated genes was determined by real-time polymerase chain reaction (PCR) technique. Results: Cell viability and colony numbers in groups exposed to secretome were significantly lower than the control group. The amount of apoptosis-related genes (Bax/Bcl-2, P53, caspase-3 and caspase-8) expression in secretome-treated groups was more than the control group. Conclusion: The data revealed that ADSCs secretome caused the significant reduction of cell growth and induced apoptosis in C-643 cells.

The ability of stem cells to differentiate into different cell types makes them a key component of healing damage in regenerative medicine. As human umbilical cord Wharton's jelly (HUCWJ) is available non-invasively, HUCWJ does not raise any ethical issues with higher differentiation potential compared to adult stem cells. With the ability to express embryonic stem cell markers, HUCWJ can be considered as a good candidate in regenerative medicine applications. The objective of this study was to find if these cells form cell aggregates with the same features as that formed by embryonic stem cells (embryoid body) and could form three germ layers.Eighteen umbilical cords were of healthy infants with parent permission. The umbilical cords were cut into small pieces and the explants were cultured. At the third passage, 1000, 5000 and 10000 cells/ 20 µL were cultured in hanging drops for 3 days. Then, they were incubated for additional 3 days in non-adhesive dishes. As the center of cell aggregates formed from 5000 and 10000 cells were darker than those formed from 1000 cells, this study focused on the aggregates formed by 1000 cells for further assessments. The immunocytochemistry and flowcytometry were performed using 3 color antibodies to detect the markers for three germ cell lineages.The immunohistochemistry data showed that the embryoid-body-like aggregates expressed a low amount of ectodermal and endodermal markers and most of the cells expressed mesodermal markers. The flowcytometry percentage of the cells in each aggregate that expressed ectodermal marker Otx2 was17.1% and endodermal marker, Sox 17 was 5.49%. The frequency of cells expressing mesodermal marker Brachyury was high (75.0%). Flowcytometry also showed the percentages by mathematical evaluation and we did this three times for our result accuracy.These aggregates mainly kept their mesenchymal state and showed a poor differentiation potential toward ectoderm and endoderm identity.