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Background: Testicular Leydig cell tumours (LCTs) are the most common type of sex cord–stromal tumour in men, representing 1%–3% of all testicular neoplasms. Among testicular sex cord–stromal tumours, CTNNB1 mutations and nuclear expression of β‐catenin have been typically associated with Sertoli cell tumour. Recent genomic analyses have shown that CTNNB1 variants are also identified in a subset of LCTs; however, the frequency and clinicopathologic associations of β‐catenin alterations remain incompletely understood in this tumour type. Methods: In this study, we evaluated 32 LCTs (five malignant/metastasizing, 27 nonmetastasizing) using β‐catenin immunohistochemistry and DNA sequencing. Results: Immunohistochemistry revealed focal or multifocal nuclear β‐catenin expression in 47% of the tumours. Diffuse nuclear β‐catenin expression (in >50% of the tumour cells) was not detected in any of the cases analysed herein. Comparison of β‐catenin‐positive and β‐catenin‐negative cases did not show significant differences in the frequency of adverse histopathologic findings or malignant clinical behaviour. DNA sequencing performed de novo on a subset of seven cases revealed the presence of exon 3 CTNNB1 variants in four of them (4/7, 57%), with variant allele frequencies (VAF) ranging from 7 to 33%. Two additional β‐catenin‐positive cases that had been sequenced as part of a previous study harboured exon 3 CTNNB1 variants at VAF of 28% and 7%, respectively. Conclusion: These results demonstrate that β‐catenin alterations are relatively common in LCT, most likely occurring as subclonal events that are not enriched in cases with aggressive features. Further studies are needed to clarify the oncogenic role of β‐catenin in this tumour type. [ABSTRACT FROM AUTHOR]

We evaluated the influence of different media plus various concentrations of Glial cell line‐derived neurotrophic factor (GDNF) during the in vitro culture (IVC) of testicular tissues from prepubertal collared peccary. Testes from 5 individuals were collected, fragmented and cultured for 28 days (34°C and 5% CO2). Culture media were Dulbecco's modified essential medium (DMEM) or stem cell serum free media (StemPro‐34™ SFM), both supplemented with various concentrations of GDNF (0, 10, or 20 ng/mL). Fragments were cultured on the flat surface of 0.75% agarose gel and were evaluated every 7 days for fragment area, histomorphology, cellular viability, and proliferative activity. Data were expressed as mean ± standard error and analyzed by Kruskal–Wallis's and Tukey test. Fragments area decreased over the 28 days‐culture, regardless of the treatment. For morphology, the StemPro‐37 SFM medium plus 10 ng/mL GDNF provided higher scores at all time points in comparison to DMEM using any GDNF concentration (p < .05). After 28 days, similar cellular viability (~70%) was observed in all treatments (p > .05). For proliferating cell nuclear antigen assay, only DMEM plus 10 ng/mL GDNF improved (p < .05) cellular proliferation on Days 14 and 28. Looking at argyrophilic nucleolar organizing regions, after 28 days, there were no differences among treatments regarding cell proliferative capacity for both spermatogonia and Sertoli cells (p > .05). In summary, the DMEM and StemPro‐34 SFM are adequate medium for IVC of prepubertal peccary testicular tissue. Supplementation with GDNF, especially at a 10 ng/mL concentration, appears to be essential for the maintenance of cell survival and proliferation. [ABSTRACT FROM AUTHOR]

Background: Spermatogenesis is a fundamental process crucial for male reproductive health and fertility. Exosomes, small membranous vesicles released by various cell types, have recently garnered attention for their role in intercellular communication. Objective: This review aims to comprehensively explore the role of exosomes in regulating spermatogenesis, focusing on their involvement in testicular development and cell‐to‐cell communication. Methods: A systematic examination of literature was conducted to gather relevant studies elucidating the biogenesis, composition, and functions of exosomes in the context of spermatogenesis. Results: Exosomes play a pivotal role in orchestrating the complex signaling networks required for proper spermatogenesis. They facilitate the transfer of key regulatory molecules between different cell populations within the testes, including Sertoli cells, Leydig cells, and germ cells. Conclusion: The emerging understanding of exosome‐mediated communication sheds light on novel mechanisms underlying spermatogenesis regulation. Further research in this area holds promise for insights into male reproductive health and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

In the orchestrated environment of the testicular niche, the equilibrium between self‐renewal and differentiation of spermatogonial stem cells (SSCs) is meticulously maintained, ensuring a stable stem cell reserve and robust spermatogenesis. Within this milieu, extracellular vesicles, specifically exosomes, have emerged as critical conveyors of intercellular communication. Despite their recognized significance, the implications of testicular exosomes in modulating SSC fate remain incompletely characterized. Given the fundamental support and regulatory influence of Sertoli cells (SCs) on SSCs, we were compelled to explore the role of SC‐derived exosomes (SC‐EXOs) in the SSC‐testicular niche. Our investigation hinged on the hypothesis that SC‐EXOs, secreted by SCs from the testes of 5‐day‐old mice—a developmental juncture marking the onset of SSC differentiation—participate in the regulation of this process. We discovered that exposure to SC‐EXOs resulted in an upsurge of PLZF, MVH, and STRA8 expression in SSC cultures, concomitant with a diminution of ID4 and GFRA1 levels. Intriguingly, obstructing exosomal communication in a SC‐SSC coculture system with the exosome inhibitor GW4869 attenuated SSC differentiation, suggesting that SC‐EXOs may modulate this process via paracrine signaling. Further scrutiny revealed the presence of miR‐493‐5p within SC‐EXOs, which suppresses Gdnf mRNA in SCs to indirectly restrain SSC differentiation through the modulation of GDNF expression—an indication of autocrine regulation. Collectively, our findings illuminate the complex regulatory schema by which SC‐EXOs affect SSC differentiation, offering novel perspectives and laying the groundwork for future preclinical and clinical investigations. [ABSTRACT FROM AUTHOR]

Carotid body tumor (CBT) is a rare neck tumor located at the adventitia of the common carotid artery bifurcation. The prominent pathological features of CBT are high vascularization and abnormal proliferation. However, single‐cell transcriptome analysis of the microenvironment composition and molecular complexity in CBT has yet to be performed. In this study, we performed single‐cell RNA sequencing (scRNA‐seq) analysis on human CBT to define the cells that contribute to hypervascularization and chronic hyperplasia. Unbiased clustering analysis of transcriptional profiles identified 16 distinct cell populations including endothelial cells (ECs), smooth muscle cells (SMCs), neuron cells, macrophage cells, neutrophil cells, and T cells. Within the ECs population, we defined subsets with angiogenic capacity plus clear signs of later endothelial progenitor cells (EPCs) to normal ECs. Two populations of macrophages were detectable in CBT, macrophage1 showed enrichment in hypoxia‐inducible factor‐1 (HIF‐1) and as well as an early EPCs cell‐like population expressing CD14 and vascular endothelial growth factor. In addition to HIF‐1‐related transcriptional protein expression, macrophages1 also display a neovasculogenesis‐promoting phenotype. SMCs included three populations showing platelet‐derived growth factor receptor beta and vimentin expression, indicative of a cancer‐associated fibroblast phenotype. Finally, we identified three types of neuronal cells, including chief cells and sustentacular cells, and elucidated their distinct roles in the pathogenesis of CBT and abnormal proliferation of tumors. Overall, our study provided the first comprehensive characterization of the transcriptional landscape of CBT at scRNA‐seq profiles, providing novel insights into the mechanisms underlying its formation. [ABSTRACT FROM AUTHOR]

Olfactory dysfunction is one of the most common symptoms of COVID‐19. In the first 2 years of the pandemic, it was frequently reported, although its incidence has significantly decreased with the emergence of the Omicron variant, which has since become the dominant viral strain. Nevertheless, many patients continue to suffer from persistent dysosmia and dysgeusia, making COVID‐19‐associated olfactory dysfunction an ongoing health concern. The proposed pathogenic mechanisms of COVID‐19‐associated olfactory dysfunction are complex and likely multifactorial. While evidence suggests that infection of sustentacular cells and associated mucosal inflammation may be the culprit of acute, transient smell loss, alterations in other components of the olfactory system (e.g., olfactory receptor neuron dysfunction, olfactory bulb injury and alterations in the olfactory cortex) may lead to persistent, long‐term olfactory dysfunction. This review aims to provide a comprehensive summary of the epidemiology, clinical manifestations and current understanding of the pathogenic mechanisms of COVID‐19‐associated olfactory dysfunction. [ABSTRACT FROM AUTHOR]

This article discusses a study that examines the impact of a high-fat diet on male fertility in mice. The researchers used single-cell RNA sequencing to analyze testis cells and found that a high-fat diet led to weight gain, glucose tolerance, and insulin resistance in the mice. The study also found that the high-fat diet impaired spermatogenesis by inhibiting testosterone synthesis through a specific pathway. Additionally, the researchers discovered that oxidized low-density lipoprotein played a role in impairing Leydig cell function. Overall, the study provides insights into the mechanisms by which a high-fat diet affects male fertility and suggests potential avenues for clinical treatment of infertility in obese men. [Extracted from the article]

Aims: Ovarian Wilms tumour (WT)/nephroblastoma is an extremely rare neoplasm that has been reported to occur in pure form or as a component of a teratomatous neoplasm. We hypothesized that teratoma‐associated and pure ovarian WT may represent different tumour types with diverging molecular backgrounds. To test this hypothesis, we comprehensively characterized a series of five tumours originally diagnosed as ovarian WT. Methods and Results: The five cases comprised three teratoma‐associated (two mature and one immature) and two pure WTs. Two of the teratoma‐associated WTs consisted of small nodular arrangements of "glandular"/epithelial structures, while the third consisted of both an epithelial and a diffuse spindle cell/blastemal component. The pure WTs consisted of "glandular" structures, which were positive for sex cord markers (including inhibin and SF1) together with a rhabdomyosarcomatous component. The two pure WTs harboured DICER1 pathogenic variants (PVs), while the three associated with teratomas were DICER1 wildtype. Panel‐based DNA sequencing of four of the cases did not identify PVs in the other genes investigated. Analysis of the HA19/IGF2 imprinting region showed retention of imprinting in the pure WTs but loss of heterozygosity with hypomethylation of the ICR1 region in two of three teratoma‐associated WTs. Furthermore, copy number variation and clustering‐based whole‐genome DNA methylation analyses identified divergent molecular profiles for pure and teratoma‐associated WTs. Conclusion: Based on the morphological features, immunophenotype, and molecular findings (DICER1 PVs, copy number, and DNA methylation profiles), we suggest that the two cases diagnosed as pure primary ovarian WT represent moderately to poorly differentiated Sertoli Leydig cell tumours (SLCTs), while the tumours arising in teratomas represent true WTs. It is possible that at least some prior cases reported as pure primary ovarian WT represent SLCTs. [ABSTRACT FROM AUTHOR]

Sertoli cells of sharks are non‐permanent components of the spermatocyst that they share exclusively with only one germ cell stage. After spermiation, all Sertoli cells, and thus the whole spent cyst, are disposed of in an area adjacent to the spermatozoal spermatocysts, that is, the resorption zone (RZ). Differences in the histology and magnitude of the RZ of the mature blue shark and Greenland shark correlate with differences in how spent cysts are dismantled. In the blue shark's RZ, the spent cyst's Sertoli nuclei were synchronously and stepwise fragmented into pyknotic bodies that were eventually resorbed in a whorl in the RZ interstitium. Conversely, cyst dismantling in the Greenland shark, that also lacked a spatially definitive RZ, revealed redundancy. One mode entailed the sloughing of the bulky Sertoli nuclei through an indistinct cyst–ductule transition area into its attached collecting ductule. A second mode entailed the asynchronous, progressive fragmentation of the bulky Sertoli nuclei into membrane‐enclosed pyknotic bodies. Both these modes solely entailed an internally coordinated demise of the spent cyst and whose basal lamina remained intact almost right to the end. Whatever the underlying mechanisms of these differences, these findings nonetheless reveal species‐specificity in the clearing up of the elasmobranch testicular parenchyma after the completion of a round of spermiogenesis. One consideration is the blue shark's expansive immune cell augmented RZ, that adjoins the animal's bone marrow equivalent tissue. The notable finding of a second conspicuous Sertoli cell type in the Greenland shark's spent cysts is also discussed. [ABSTRACT FROM AUTHOR]

Busulfan is an antineoplastic, which is always accompanied with the abnormal of spermatogonia self‐renewal and differentiation. It has been demonstrated that the omega‐3 polyunsaturated fatty acids (PUFAs) benefits mature spermatozoa. However, whether omega‐3 can protect endogenous spermatogonia and the detailed mechanisms are still unclear. Evaluate of spermatogenesis function (in vivo) were examined by histopathological analysis, immunofluorescence staining, and western blotting. The levels of lipid metabolites in testicular tissue were determined via liquid chromatography. We investigated the effect of lipid metabolites on Sertoli cells provided paracrine factors to regulate spermatogonia proliferation and differentiation using co‐culture system. In our study, we showed that omega‐3 PUFAs significantly improved the process of sperm production and elevated the quantity of both undifferentiated Lin28+ spermatogonia and differentiated c‐kit+ spermatogonia in a mouse model where spermatogenic function was disrupted by busulfan. Mass spectrometry revealed an increase in the levels of several omega‐3 metabolites in the testes of mice fed with omega‐3 PUFAs. The eicosapentaenoic acid metabolite 12‐hydroxyeicosapentaenoic acid (12‐HEPE) up‐regulated bone morphogenic protein 4 (BMP4) expression through GPR120‐ERK1/2 pathway activation in Sertoli cells and restored spermatogonia proliferation and differentiation. Our study provides evidence that omega‐3 PUFAs metabolite 12‐HEPE effectively protects spermatogonia and reveals that GPR120 might be a tractable pharmacological target for fertility in men received chemotherapy or severe spermatogenesis dysfunction. [ABSTRACT FROM AUTHOR]

A study published in Clinical & Translational Medicine examines the potential benefits of paeonol in treating spermatogenesis disorders in diabetic patients. The study reveals that diabetes can negatively impact male reproductive function by increasing the production of reactive oxygen species (ROS). The researchers discovered that a protein called SIRT3, which helps maintain redox balance, plays a crucial role in spermatogenesis. Paeonol, a compound found in peony bark, was found to increase SIRT3 levels and reduce oxidative stress in testicular tissues and cells treated with high glucose. In diabetic rat models, paeonol administration improved sperm quality and reduced testicular damage. These findings suggest that paeonol may be a potential therapeutic option for individuals with diabetes-related spermatogenic dysfunction. [Extracted from the article]

Lambda light chains (λ‐LCs) are frequently responsible for triggering the activation of inflammatory factors in autoimmune disorders, and an increase in their levels will cause various pathological changes in serum. The aim of this study was to determine the histological differences between the epididymis and testis of normal and cryptorchid Bactrian camels and the differences in λ‐LC expression in the epididymis and testis of normal and cryptorchid Bactrian camels. Haematoxylin and eosin (H&E) staining was used to examine the pathological changes in cryptorchidism. The gene and protein levels of λ‐LC were determined using RT‐qPCR and western blot. The distribution of λ‐LCs was assessed by immunohistochemistry and immunofluorescence. Compared with that in normal Bactrian camels, the diameter of the epididymal lumen and the thickness of the epithelium were decreased in the epididymis of cryptorchidic animals. Additionally, no sperm was detected in the cavity of the cryptorchidic epididymis. Meanwhile, the expression of λ‐LC was significantly increased in the cryptorchidic epididymis at both the mRNA and protein levels (p <.05). The highest protein expression of λ‐LC was found in epididymal epithelial halo cells and testicular Sertoli cells. These findings suggested that the structural changes observed in the epididymal epithelium of cryptorchidic camels affect its secretory and absorptive functions. Additionally, the high level of λ‐LC expression recorded in halo cells suggested that these cells play an important role in epithelial immunity in cryptorchidic Bactrian camels. Furthermore, the high λ‐LC expression levels detected in normal testicular Sertoli cells indicated that λ‐LCs may be involved in spermatogenesis. The results of this study provide clues for an in‐depth study of immunological sterility in cryptorchidic Bactrian camels. [ABSTRACT FROM AUTHOR]