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Background Objectives Materials and methods Results and conclusion Spermatogonial stem cells (SSCs) are essential for adult spermatogenesis. Themolecular mechanisms driving SSC generation are poorly understood.Zou et al. reported that the precursor cells that give rise to SSCs–prospermatogonia (ProSG) require the RNA‐binding protein, DDX20, in orderto undergo the obligatory proliferative re‐activation step that proceeds SSC formation.Literature search.We summarize the authors' discovery that the RNA‐binding protein, DDX20, iscritical for driving the proliferative re‐activation of ProSG, a key step that proceeds SSC generation in vivo. They provide evidence that DDX20 performs this role through its ability to promote the translation of mRNAs encoding proteins known to be essential for cell‐cycle and spermatogonial homeostasis. It remains to be determined whether this role is conserved inhumans. It will also be interesting to elucidate whether other post‐transcriptional regulators also have roles in early germ cell development. More broadly, it will be fascinating to determine whether post‐transcriptional regulators workin concert with transcriptional regulators to drive germ‐cell development. [ABSTRACT FROM AUTHOR]

The mitotic quiescence of prospermatogonia is the event known to occur during genesis of the male germline and is tied to the development of the spermatogenic lineage. The regulatory mechanisms and the functional importance of this process have been demonstrated in mice; however, regulation of this process in human and domestic animal is still largely unknown. In this study, we employed single‐cell RNA sequencing to identify transcriptional signatures of prospermatogonia and major somatic cell types in testes of goats at E85, E105, and E125. We identified both common and specific Gene Ontology categories, transcription factor regulatory networks, and cell–cell interactions in cell types from goat testis. We also analyzed the transcriptional dynamic changes in prospermatogonia, Sertoli cells, Leydig cells, and interstitial cells. Our datasets provide a useful resource for the study of domestic animal germline development. [ABSTRACT FROM AUTHOR]

In the developing mammalian testis, only a small proportion of fetal and neonatal prospermatogonia give rise to the foundational pool of spermatogonial stem cells (SSCs). Multiple lines of evidence have suggested the determination of which prospermatogonia give rise to foundational SSCs is not random, but is rather predetermined, such that foundational SSCs are ensured to develop advantageous characteristics such as enhanced genetic integrity. Here I suggest that differential epigenetic programing contributes to the molecular mechanisms by which an early subset of developing prospermatogonia becomes predetermined to form the foundational pool of SSCs. This would include epigenetic programing that promotes active expression of genes needed to develop advantageous characteristics, as well as differential epigenetic priming, which bookmarks genes that comprise the SSC‐specific transcriptome to become activated when foundational SSCs appear in the postnatal testis. I suggest that, together, differential epigenetic programing and epigenetic priming contribute to the molecular mechanisms by which an early subset of developing prospermatogonia becomes predetermined to form the foundational pool of SSCs. [ABSTRACT FROM AUTHOR]

Germplasm cryopreservation and expansion of gonocytes/prospermatogonia or spermatogonial stem cells (SSCs) are important; however, it's difficult in cattle. Since inhibitors of Mek1/2 and Gsk3β (2i) can enhance pluripotency maintenance, effects of 2i‐based medium on the cultivation of bovine prospermatogonia from the cryopreserved tissues were examined. The testicular tissues of newborn bulls were well cryopreserved. High mRNA levels of prospermatogonium/SSC markers (PLZF, GFRα‐1) and pluripotency markers (Oct4/Pouf5, Sox2, Nanog) were detected and the PLZF+/GFRα‐1+ prospermatogonia were consistently identified immunohistochemically in the seminiferous cords. Using differential plating and Percoll‐based centrifugation, 41.59% prospermatogonia were enriched and they proliferated robustly in 2i medium. The 2i medium boosted mRNA abundances of Pouf5, Sox2, Nanog, GFRα‐1, PLZF, anti‐apoptosis gene Bcl2, LIF receptor gene LIFR and enhanced PLZF protein expression, but suppressed mRNA expressions of spermatogonial differentiation marker c‐kit and pro‐apoptotic gene Bax, in the cultured prospermatogonia. It also alleviated H2O2‐induced apoptosis of the enriched cells and decreased histone H3 lysine (K9) trimethylation (H3K9me3) and its methylase Suv39h1/2 mRNA level in the cultured seminiferous cords. Overall, 2i medium improves the cultivation of bovine prospermatogonia isolated from the cryopreserved testes, by inhibiting Suv39h1/2‐mediated H3K9me3 through Mek1/2 and Gsk3β signalling, evidencing successful cryopreservation and expansion of bovine germplasm. [ABSTRACT FROM AUTHOR]

Despite the importance of germ cell (GC) differentiation for sexual reproduction, the gene networks underlying their fate remain unclear. Here, we comprehensively characterize the gene expression dynamics during sex determination based on single‐cell RNA sequencing of 14 914 XX and XY mouse GCs between embryonic days (E) 9.0 and 16.5. We found that XX and XY GCs diverge transcriptionally as early as E11.5 with upregulation of genes downstream of the bone morphogenic protein (BMP) and nodal/Activin pathways in XY and XX GCs, respectively. We also identified a sex‐specific upregulation of genes associated with negative regulation of mRNA processing and an increase in intron retention consistent with a reduction in mRNA splicing in XY testicular GCs by E13.5. Using computational gene regulation network inference analysis, we identified sex‐specific, sequential waves of putative key regulator genes during GC differentiation and revealed that the meiotic genes are regulated by positive and negative master modules acting in an antagonistic fashion. Finally, we found that rare adrenal GCs enter meiosis similarly to ovarian GCs but display altered expression of master genes controlling the female and male genetic programs, indicating that the somatic environment is important for GC function. Our data are available on a web platform and provide a molecular roadmap of GC sex determination at single‐cell resolution, which will serve as a valuable resource for future studies of gonad development, function, and disease. [ABSTRACT FROM AUTHOR]

Background: The germline serves as a conduit for transmission of genetic and epigenetic information from one generation to the next. In males, spermatozoa are the final carriers of inheritance and their continual production is supported by a foundational population of spermatogonial stem cells (SSCs) that forms from prospermatogonial precursors during the early stages of neonatal development. In mammals, the timing for which SSCs are specified and the underlying mechanisms guiding this process remain to be completely understood. Objectives: To propose an evolving concept for how the foundational SSC population is established. Materials and methods: This review summarizes recent and historical findings from peer‐reviewed publications made primarily with mouse models while incorporating limited studies from humans and livestock. Results and conclusion: Establishment of the SSC population appears to follow a biphasic pattern involving a period of fate programming followed by an establishment phase that culminates in formation of the SSC population. This model for establishment of the foundational SSC population from precursors is anticipated to extend across mammalian species and include humans and livestock, albeit on different timescales. [ABSTRACT FROM AUTHOR]