Retinoic acid regulates sex-specific timing of meiotic initiation in mice

Jana Koubova; Douglas B Menke; Qing Zhou; Blanche Capel; Michael D Griswold; David C Page

doi:10.1073/pnas.0510813103

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Retinoic acid regulates sex-specific timing of meiotic initiation in mice

Journal article

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Retinoic acid regulates sex-specific timing of meiotic initiation in mice

Jana Koubova, Douglas B Menke, Qing Zhou, Blanche Capel, Michael D Griswold and David C Page

Proceedings of the National Academy of Sciences - PNAS, Vol.103(8), pp.2474-2479

02/21/2006

DOI: https://doi.org/10.1073/pnas.0510813103

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https://hdl.handle.net/2376/113059

PMCID: PMC1413806

PMID: 16461896

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Abstract

Testis - metabolism

Retinoic Acid 4-Hydroxylase

Ovary - embryology

Vitamin A Deficiency - metabolism

Cytochrome P-450 Enzyme System - metabolism

Male

Meiosis

Testis - drug effects

Adaptor Proteins, Signal Transducing

Animals

Proteins - metabolism

Sex Determination Processes

Testis - embryology

Time Factors

Tretinoin - metabolism

Female

Ovary - drug effects

Mice

Tretinoin - physiology

Ovary - metabolism

Tretinoin - pharmacology

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 G0/G1 mitotic cell cycle arrest, and meiosis begins after birth. In mice, the Stimulated by Retinoic Acid Gene 8 (Stra8) has been found to be required for the transition into meiosis in both female and male germ cells. Stra8 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 Stra8 expression and meiotic initiation in mice. Our work shows that signaling by retinoic acid (RA), an active derivative of vitamin A, is required for Stra8 expression and thereby meiotic initiation in embryonic ovaries. We also discovered that RA is sufficient to induce Stra8 expression in embryonic testes and in vitamin A-deficient adult testes in vivo. Finally, our results show that cytochrome p450 (CYP)-mediated RA metabolism prevents premature Stra8 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 Stra8 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 Stra8 expression in both embryonic ovaries and adult testes, this portion of the meiotic initiation pathway may be identical in both sexes.

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Title: Retinoic acid regulates sex-specific timing of meiotic initiation in mice
Creators: Jana Koubova - Howard Hughes Medical Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
Douglas B Menke
Qing Zhou
Blanche Capel
Michael D Griswold
David C Page
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.103(8), pp.2474-2479
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: R37 HD010808 / NICHD NIH HHS HD39963 / NICHD NIH HHS R01 HD010808 / NICHD NIH HHS R01 HD039963 / NICHD NIH HHS R37 HD039963 / NICHD NIH HHS HD10808 / NICHD NIH HHS
Identifiers: 99900548285001842
Language: English
Resource Type: Journal article