Ovary-specific depletion of the nuclear receptor Nr5a2 compromises expansion of the cumulus oophorus but not fertilization by intracytoplasmic sperm injection

Biology of Reproduction
Kalyne BertolinBruce D Murphy

Abstract

The orphan nuclear receptor, liver receptor homolog-1 (aka Nuclear receptor subfamily 5, Group A, Member 2 (Nr5a2)), is widely expressed in mammalian tissues, and its ovarian expression is restricted to granulosa cells of activated follicles. We employed the floxed Nr5a2 (Nr5a2f/f) mutant mouse line and two granulosa-specific Cre lines, Anti-Müllerian hormone receptor- 2 (Amhr2Cre) and transgenic cytochrome P450 family 19 subfamily A polypeptide 1 (tgCyp19Cre), to develop two tissue- and time-specific Nr5a2 depletion models: Nr5a2Amhr2-/- and Nr5a2Cyp19-/-. In the Nr5a2Cyp19-/- ovaries, Nr5a2 was depleted in mural granulosa, but not cumulus cells. We induced follicular development in mutant and wild-type (control, CON) mice with equine chorionic gonadotropin followed 44 h later treatment with human chorionic gonadotropin (hCG) to induce ovulation. Both Nr5a2Amhr2-/- and Nr5a2Cyp19-/- cumulus-oocyte complexes underwent a reduced degree of expansion in vitro relative to wild-type mice. We found downregulation of epiregulin (Ereg), amphiregulin (Areg), betacellulin (Btc) and tumor necrosis factor stimulated gene-6 (Tnfaip6) transcripts in Nr5a2Amhr2-/- and Nr5a2Cyp19-/- ovaries. Tnfaip6 protein abundance, by quantitative immunoflu...Continue Reading

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Citations

Feb 15, 2019·Reproduction, Fertility, and Development·Thais A RodriguesF F Paula-Lopes
Oct 23, 2019·Molecular Reproduction and Development·Yu ZhangMeijia Zhang
Mar 12, 2021·G3 : Genes - Genomes - Genetics·Allison N BeachumElizabeth T Ables
Dec 9, 2020·Molecular Aspects of Medicine·Camilla H K Hughes, Bruce D Murphy
Dec 21, 2021·Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology·Yue-Wei LiZhi-Yi Chen

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