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Dev Biol. 2017 Apr 15;424(2):208-220. doi: 10.1016/j.ydbio.2017.02.015. Epub 2017 Mar 6.

Retinoic acid signaling is dispensable for somatic development and function in the mammalian ovary.

Author information

1
Department of Genetics, Cell Biology, and Development, and Developmental Biology Center, University of Minnesota, Minneapolis, MN 55455, USA.
2
Université Cote d'Azur, Inserm, CNRS, iBV, F-06108 Nice, France.
3
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS (UMR7104), INSERM U964, Université de Strasbourg, F-67404 Illkirch, France.
4
Department of Genetics, Cell Biology, and Development, and Developmental Biology Center, University of Minnesota, Minneapolis, MN 55455, USA; University of Minnesota Masonic Cancer Center, Minneapolis, MN 55455, USA.
5
Department of Genetics, Cell Biology, and Development, and Developmental Biology Center, University of Minnesota, Minneapolis, MN 55455, USA; University of Minnesota Masonic Cancer Center, Minneapolis, MN 55455, USA. Electronic address: zarko001@umn.edu.

Abstract

Retinoic acid (RA) is a potent inducer of cell differentiation and plays an essential role in sex-specific germ cell development in the mammalian gonad. RA is essential for male gametogenesis and hence fertility. However, RA can also disrupt sexual cell fate in somatic cells of the testis, promoting transdifferentiation of male Sertoli cells to female granulosa-like cells when the male sexual regulator Dmrt1 is absent. The feminizing ability of RA in the Dmrt1 mutant somatic testis suggests that RA might normally play a role in somatic cell differentiation or cell fate maintenance in the ovary. To test for this possibility we disrupted RA signaling in somatic cells of the early fetal ovary using three genetic strategies and one pharmaceutical approach. We found that deleting all three RA receptors (RARs) in the XX somatic gonad at the time of sex determination did not significantly affect ovarian differentiation, follicle development, or female fertility. Transcriptome analysis of adult triple mutant ovaries revealed remarkably little effect on gene expression in the absence of somatic RAR function. Likewise, deletion of three RA synthesis enzymes (Aldh1a1-3) at the time of sex determination did not masculinize the ovary. A dominant-negative RAR transgene altered granulosa cell proliferation, likely due to interference with a non-RA signaling pathway, but did not prevent granulosa cell specification and oogenesis or abolish fertility. Finally, culture of fetal XX gonads with an RAR antagonist blocked germ cell meiotic initiation but did not disrupt sex-biased gene expression. We conclude that RA signaling, although crucial in the ovary for meiotic initiation, is not required for granulosa cell specification, differentiation, or reproductive function.

KEYWORDS:

DMRT1; Granulosa; Ovary; Retinoic acid; Sertoli

PMID:
28274610
PMCID:
PMC5411265
DOI:
10.1016/j.ydbio.2017.02.015
[Indexed for MEDLINE]
Free PMC Article

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