ArticleProceedings of the National Academy of Sciences of the United States of America2012
Retinoic acid induces Sertoli cell paracrine signals for spermatogonia differentiation but cell autonomously drives spermatocyte meiosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
122 citing papers in PubMed, 1 synthesis or guideline pooled it, 224 citations in OpenAlex.
- Metabolic transitions define spermatogonial stem cell maturation.Human reproduction (Oxford, England) · 2022Pooled it
- Associations of Bovine Fetal Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Germ Cell Marker Expression in Testicular Organoids.Animals : an open access journal from MDPI · 2026Article
- Article
- Reviewing the Implication of Aldehyde Dehydrogenases in Male Reproduction: Prospects for New Therapeutic Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A single-cell multiomics roadmap of zebrafish spermatogenesis reveals regulatory principles of male germline formation.Molecular systems biology · 2026Article
- Effects of Aging on Mammalian Spermatogenesis From a Cellular Perspective.Molecular reproduction and development · 2025Review
- Kinetics of the inhibition and recovery of spermatogenesis induced by treatment with WIN 18,446, a male contraceptive, in mice.Andrology · 2025Article
- Histological analysis of cheetah testes focused on the germ cells and Sertoli cells.The Journal of veterinary medical science · 2025Article
- The circadian clock orchestrates spermatogonial differentiation and fertilization by regulating retinoic acid signaling in vertebrates.National science review · 2025Article
- The effect of induced molting on the testicular physiological remodeling in no-semen roosters.BMC genomics · 2025Article
- The interplay between retinoic acid binding proteins and retinoic acid degrading enzymes in modulating retinoic acid concentrations.Current topics in developmental biology · 2025Review
- Inhibiting Aldehyde Dehydrogenase Function Using WIN 18,446 to Synchronize Spermatogenesis.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Sertoli cells as a hub in testicular development and male reproductive.Frontiers in cell and developmental biology · 2025Review
- The Biology and Regulation of Spermatogonial Stem Cells in the Niche.Advances in experimental medicine and biology · 2025Review
- Differential Impairment Mechanism of Sperm Production via Induction of miR-34c-Activated Apoptosis and Spermatogenesis Pathway in Diet-Induced Obesity and Resistant Mice and GC-1 Spg Cells.International journal of molecular sciences · 2024Article
- Review
- PRC1 directs PRC2-H3K27me3 deposition to shield adult spermatogonial stem cells from differentiation.Nucleic acids research · 2024Article
- Targeting nuclear receptor corepressors for reversible male contraception.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The immunomodulatory role of all-trans retinoic acid in tumor microenvironment.Clinical and experimental medicine · 2023Review
- Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Direct evidence for a role of endogenous retinoic acid (RA), the active metabolite of vitamin A in the initial differentiation and meiotic entry of spermatogonia, and thus in the initiation of spermatogenesis is still lacking. RA is synthesized by dedicated enzymes, the retinaldehyde dehydrogenases (RALDH), and binds to and activates nuclear RA receptors (RARA, RARB, and RARG) either within the RA-synthesizing cells or in the neighboring cells. In the present study, we have used a combination of somatic genetic ablations and pharmacological approaches in vivo to show that during the first, prepubertal, spermatogenic cycle (i) RALDH-dependent synthesis of RA by Sertoli cells (SC), the supporting cells of the germ cell (GC) lineage, is indispensable to initiate differentiation of A aligned into A1 spermatogonia; (ii) RARA in SC mediates the effects of RA, possibly through activating Mafb expression, a gene whose Drosophila homolog is mandatory to GC differentiation; (iii) RA synthesized by premeiotic spermatocytes cell autonomously induces meiotic initiation through controlling the RAR-dependent expression of Stra8. Furthermore, we show that RA of SC origin is no longer necessary for the subsequent spermatogenic cycles but essential to spermiation. Altogether, our data establish that the effects of RA in vivo on spermatogonia differentiation are indirect, via SC, but direct on meiotic initiation in spermatocytes, supporting thereby the notion that, contrary to the situation in the female, RA is necessary to induce meiosis in the male.
Indexed as
Identifiers
What OpenQuestion holds
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.