ArticleDevelopmental biology2015
Mammalian target of rapamycin complex 1 (mTORC1) Is required for mouse spermatogonial differentiation in vivo.
Article in Developmental biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 92 citations in OpenAlex.
- Rapamycin co-exposure fails to reduce cisplatin-induced damage in GC6-spg spermatogonial cell line.Reproduction & fertility · 2026Article
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- The therapeutic potential of Zuogui Wan in oligoasthenozoospermia: insights from network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation.Scientific reports · 2025Article
- Comparative genomics of two closely related Acropora coral species with different spawning seasons reveals genomic regions possibly associated with gametogenesis.BMC ecology and evolution · 2025Article
- Histological analysis of cheetah testes focused on the germ cells and Sertoli cells.The Journal of veterinary medical science · 2025Article
- PPP6R3-mediated dephosphorylation regulates mRNA translation during spermatogonial differentiation.Communications biology · 2025Article
- Insulin‑like growth factor 2 in spermatogenesis dysfunction (Review).Molecular medicine reports · 2025Review
- Autophagy accompanying the developmental process of male germline stem cells.Cell and tissue research · 2024Review
- Targeting dysregulated phago-/auto-lysosomes in Sertoli cells to ameliorate late-onset hypogonadism.Nature aging · 2024Article
- Review
- mTORC1 is required for differentiation of germline stem cells in the Drosophila melanogaster testis.PloS one · 2024Article
- Neonatal vitamin A supplementation improves sheep fertility potential.Frontiers in veterinary science · 2024Article
- Comprehensive Analysis of the Transcriptome-Wide mInternational journal of molecular sciences · 2023Article
- Decoding the spermatogonial stem cell niche under physiological and recovery conditions in adult mice and humans.Science advances · 2023Article
- Differential responsiveness of spermatogonia to retinoic acid dictates precocious differentiation but not meiotic entry during steady-state spermatogenesis†.Biology of reproduction · 2023Article
- Review
- The Role of Promyelocytic Leukemia Zinc Finger (PLZF) and Glial-Derived Neurotrophic Factor Family Receptor Alpha 1 (GFRα1) in the Cryopreservation of Spermatogonia Stem Cells.International journal of molecular sciences · 2023Review
- Pharmacological Treatment of Neonatal and Juvenile Mice to Study Spermatogenesis.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Autophagy: A Double-Edged Sword in Male Reproduction.International journal of molecular sciences · 2022Review
- How does retinoic acid (RA) signaling pathway regulate spermatogenesis?Histology and histopathology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Spermatogonial stem cells (SSCs) must balance self-renewal with production of transit-amplifying progenitors that differentiate in response to retinoic acid (RA) before entering meiosis. This self-renewal vs. differentiation spermatogonial fate decision is critical for maintaining tissue homeostasis, as imbalances cause spermatogenesis defects that can lead to human testicular cancer or infertility. A great deal of effort has been exerted to understand how the SSC population is maintained. In contrast, little is known about the essential program of differentiation initiated by retinoic acid (RA) that precedes meiosis, and the pathways and proteins involved are poorly defined. We recently reported a novel role for RA in stimulating the PI3/AKT/mTOR kinase signaling pathway to activate translation of repressed mRNAs such as Kit. Here, we examined the requirement for mTOR complex 1 (mTORC1) in mediating the RA signal to direct spermatogonial differentiation in the neonatal testis. We found that in vivo inhibition of mTORC1 by rapamycin blocked spermatogonial differentiation, which led to an accumulation of undifferentiated spermatogonia. In addition, rapamycin also blocked the RA-induced translational activation of mRNAs encoding KIT, SOHLH1, and SOHLH2 without affecting expression of STRA8. These findings highlight dual roles for RA in germ cell development - transcriptional activation of genes, and kinase signaling to stimulate translation of repressed messages required for spermatogonial differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.