Retinoic acid disrupts cumulus granulosa cells function via EGFR downregulation: induction of PCOS and infertility in adult female mice.

چکیده اصلی

Polycystic ovarian syndrome (PCOS) is a prevalent metabolic and neuroendocrine disease affecting females of childbearing age. Irregular ovulation, elevated androgen levels, and the presence of multiple ovarian cysts characterize it. This study aimed to investigate the prolonged impact of RA on female fertility during three oestrus cycles, utilizing biochemical, histopathological, and immunohistochemical analyses. Twelve female mice were classified into two groups of 6 animals each: (1) the negative control group that received DMSO diluted with sunflower oil, and (2) the positive control group that received a 10 mg/kg dose of retinoic acid. For 15 days, intraperitoneal injections were given daily. The animals were physically euthanized by slaughter on day 16 after treatment. Histopathological and immunohistochemical expression of EGFR, as well as hormonal level investigations, including FSH and LH, were performed on day 16. A 10 mg/kg RA daily dose for 15 days significantly induces FSH and reduces LH. In addition, we revealed that exogenous excess RA leads to PCOS, which causes an increase in cystic follicles and a reduction in antral follicles and corpus luteum. Immunohistochemically, excessive RA suppresses the expression of EGFR, which is localized in granulosa cells. Our investigation concluded that inhibition of epidermal growth factor receptor (EGFR) signaling resulting from long-term high-dose treatment with retinoic acid (RA) affects cumulus granulosa cell proliferation and oocyte maturation. So, vitamin A may harm female fertility.

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