期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 41, 页码 16582-16587出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1214936109
关键词
mouse; mutagenesis; retinoid antagonist; RAR/RXR heterodimer
资金
- Centre National de la Recherche Scientifique, Institut National de la Sante et de la Recherche Medicale, Hopital Universitaire de Strasbourg
- Fondation pour la Recherche Medicale (FRM) [DEQ20071210544]
- Agence Nationale de la Recherche [ANR-09-BLAN-0286, ANR-10-BLAN-1239-04, ANR-09-BLAN-0282]
- French Ministry of Research and Technology
- FRM Grant [FDT20110922849]
- Agence Nationale de la Recherche (ANR) [ANR-09-BLAN-0282, ANR-09-BLAN-0286, ANR-10-BLAN-1239] Funding Source: Agence Nationale de la Recherche (ANR)
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.
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