Deletion of RhoA in Progesterone Receptor-Expressing Cells Leads to Luteal Insufficiency and Infertility in Female Mice

Endocrinology
Ahmed E El ZowalatyXiaoqin Ye

Abstract

Ras homolog gene family, member A (RhoA) is widely expressed throughout the female reproductive system. To assess its role in progesterone receptor-expressing cells, we generated RhoA conditional knockout mice RhoAd/d (RhoAf/f-Pgr-Cre+/-). RhoAd/d female mice had comparable mating activity, serum luteinizing hormone, prolactin, and estradiol levels and ovulation with control but were infertile with progesterone insufficiency, indicating impaired steroidogenesis in RhoAd/d corpus luteum (CL). RhoA was highly expressed in wild-type luteal cells and conditionally deleted in RhoAd/d CL. Gestation day 3.5 (D3.5) RhoAd/d ovaries had reduced numbers of CL, less defined corpus luteal cord formation, and disorganized CL collagen IV staining. RhoAd/d CL had lipid droplet and free cholesterol accumulation, indicating the availability of cholesterol for steroidogenesis, but disorganized β-actin and vimentin staining, indicating disrupted cytoskeleton integrity. Cytoskeleton is important for cytoplasmic cholesterol movement to mitochondria and for regulating mitochondria. Dramatically reduced expression of mitochondrial markers heat shock protein 60 (HSP60), voltage-dependent anion channel, and StAR was detected in RhoAd/d CL. StAR carries ...Continue Reading

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Citations

May 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Diana MonsivaisMartin M Matzuk
Jun 16, 2019·Biology of Reproduction·Manjunatha K NanjappaPaul S Cooke
Nov 1, 2017·Biology of Reproduction·Ahmed E El Zowalaty, Xiaoqin Ye
Jul 2, 2020·Molecular and Cellular Endocrinology·Natalie A DeWittAmanda N Kallen
Sep 24, 2021·Biology of Reproduction·Christian Lee AndersenXiaoqin Ye

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