{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T09:10:59Z","timestamp":1793524259051,"version":"4.5.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,2,21]]},"abstract":"<jats:p>\n                    In mammals, meiosis is initiated at different time points in males and females, but the mechanism underlying this difference is unknown. Female germ cells begin meiosis during embryogenesis. In males, embryonic germ cells undergo G\n                    <jats:sub>0<\/jats:sub>\n                    \/G\n                    <jats:sub>1<\/jats:sub>\n                    mitotic cell cycle arrest, and meiosis begins after birth. In mice, the\n                    <jats:italic>Stimulated by Retinoic Acid Gene 8<\/jats:italic>\n                    (\n                    <jats:italic>Stra8<\/jats:italic>\n                    ) has been found to be required for the transition into meiosis in both female and male germ cells.\n                    <jats:italic>Stra8<\/jats:italic>\n                    is expressed in embryonic ovaries just before meiotic initiation, whereas its expression in testes is first detected after birth. Here we examine the mechanism underlying the sex-specific timing of\n                    <jats:italic>Stra8<\/jats:italic>\n                    expression and meiotic initiation in mice. Our work shows that signaling by retinoic acid (RA), an active derivative of vitamin A, is required for\n                    <jats:italic>Stra8<\/jats:italic>\n                    expression and thereby meiotic initiation in embryonic ovaries. We also discovered that RA is sufficient to induce\n                    <jats:italic>Stra8<\/jats:italic>\n                    expression in embryonic testes and in vitamin A-deficient adult testes\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Finally, our results show that cytochrome p450 (CYP)-mediated RA metabolism prevents premature\n                    <jats:italic>Stra8<\/jats:italic>\n                    expression in embryonic testes. Treatment with an inhibitor specific to RA-metabolizing enzymes indicates that a cytochrome p450 from the 26 family (CYP26) is responsible for delaying\n                    <jats:italic>Stra8<\/jats:italic>\n                    expression in embryonic testes. Sex-specific regulation of RA signaling thus plays an essential role in meiotic initiation in embryonic ovaries and precludes its occurrence in embryonic testes. Because RA signaling regulates\n                    <jats:italic>Stra8<\/jats:italic>\n                    expression in both embryonic ovaries and adult testes, this portion of the meiotic initiation pathway may be identical in both sexes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0510813103","type":"journal-article","created":{"date-parts":[[2006,2,6]],"date-time":"2006-02-06T20:33:05Z","timestamp":1139257985000},"page":"2474-2479","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":876,"title":["Retinoic acid regulates sex-specific timing of meiotic initiation in mice"],"prefix":"10.1073","volume":"103","author":[{"given":"Jana","family":"Koubova","sequence":"first","affiliation":[{"name":"*Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas B.","family":"Menke","sequence":"additional","affiliation":[{"name":"*Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for Reproductive Biology, School of Molecular Biosciences, Washingston State University, Pullman, WA 99164; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanche","family":"Capel","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Duke University Medical Center, Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Griswold","sequence":"additional","affiliation":[{"name":"Center for Reproductive Biology, School of Molecular Biosciences, Washingston State University, Pullman, WA 99164; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Page","sequence":"additional","affiliation":[{"name":"*Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,2,6]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"7","volume":"38","author":"McLaren A.","year":"1984","unstructured":"A. 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