Humdia
Ahmad
Characterization of Two Retinoic Acid Receptor Alpha Conditional Knockout Mouse Models
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Authors:
Humdia Ahmad
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The ovaries are the primary endocrine and reproductive organs in females. The ovarian follicle is the basic structural and functional unit of the ovary. When there is abnormal development in ovarian follicles, infertility and reproductive diseases such as polycystic ovarian syndrome (PCOS), premature ovarian failure (POF), and ovarian cancers may occur. Retinoic acid (RA), a biologically active derivative of vitamin A, is a signaling molecule that plays a vital role in various physiological processes, including embryonic development, tissue differentiation, and reproduction. We have previously shown that RA stimulates granulosa cell proliferation through a cell signaling cascade involving Retinoic Acid Receptors (RARs), which have three isoforms alpha, beta, and gamma, in which alpha is the most predominant in the mouse ovary. In this study, we characterized two retinoic acid receptor alpha conditional knockout (RARA KO) mouse models with RARA deleted in granulosa cells during embryonic development using the Cre-Lox system. The uterus weights of the NC/FR RARA KO mice were decreased at both week 7 and week 15 and the body weight was increased at week 15. The NC/FR KO and UIC/FR KO animals were either sub-fertile or infertile. In addition, a variety of ovarian pathologies were observed in the NC/FR KO mice, including the presence of multi-oocyte and atretic follicles, decreased mature follicles, and overall abnormal follicle counts compared to control mice. Overall, this study provides evidence of the involvement of retinoic acid signaling, mediated by RARA, in normal ovarian development and fertility. This study will help better understand the prevention and treatment of ovarian diseases.
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DePaul University
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Co-authors:
Humdia Ahmad