ArticleBiology of reproduction2023
Differential responsiveness of spermatogonia to retinoic acid dictates precocious differentiation but not meiotic entry during steady-state spermatogenesis†.
Article in Biology of reproduction, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Reviewing the Implication of Aldehyde Dehydrogenases in Male Reproduction: Prospects for New Therapeutic Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Spermatogenesis Beyond DNA: Integrated RNA Control of the Epitranscriptome and Three-Dimensional Genome Architecture.Current issues in molecular biology · 2026Review
- Regulation of early gonocyte differentiation in zebrafish.Biochemical Society transactions · 2025Article
- L-2-hydroxyglutarate regulates centromere and heterochromatin conformation in the male germline.PLoS genetics · 2025Article
- Programming for Meiotic Competence in Mouse Male Germ Cells is Established at the Perinatal Precursor Stage of Development.Molecular reproduction and development · 2025Article
- The Biology and Regulation of Spermatogonial Stem Cells in the Niche.Advances in experimental medicine and biology · 2025Review
- Destabilization of mRNAs enhances competence to initiate meiosis in mouse spermatogenic cells.Development (Cambridge, England) · 2024Article
- SPRY4-dependent ERK negative feedback demarcates functional adult stem cells in the male mouse germline†.Biology of reproduction · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The foundation of mammalian spermatogenesis is provided by undifferentiated spermatogonia, which comprise of spermatogonial stem cells (SSCs) and transit-amplifying progenitors that differentiate in response to retinoic acid (RA) and are committed to enter meiosis. Our laboratory recently reported that the foundational populations of SSCs, undifferentiated progenitors, and differentiating spermatogonia are formed in the neonatal testis in part based on their differential responsiveness to RA. Here, we expand on those findings to define the extent to which RA responsiveness during steady-state spermatogenesis in the adult testis regulates the spermatogonial fate. Our results reveal that both progenitor and differentiating spermatogonia throughout the testis are capable of responding to exogenous RA, but their resulting fates were quite distinct-undifferentiated progenitors precociously differentiated and proceeded into meiosis on a normal timeline, while differentiating spermatogonia were unable to hasten their entry into meiosis. This reveals that the spermatogonia responding to RA must still complete the 8.6 day differentiation program prior to their entry into meiosis. Addition of exogenous RA enriched testes with preleptotene and pachytene spermatocytes one and two seminiferous cycles later, respectively, supporting recent clinical studies reporting increased sperm production and enhanced fertility in subfertile men on long-term RA analog treatment. Collectively, our results reveal that a well-buffered system exists within mammalian testes to regulate spermatogonial RA exposure, that exposed undifferentiated progenitors can precociously differentiate, but must complete a normal-length differentiation program prior to entering meiosis, and that daily RA treatments increased the numbers of advanced germ cells by directing undifferentiated progenitors to continuously differentiate.
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