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Gestational Progesterone Restores Menstrual Cycle in PCOS Patients via Enhancing Ovary Estrogen Production
24 Pages Posted: 2 Dec 2024
More...Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, typically characterized by irregular menstrual cycles. Our study found that postpartum menstrual cycles were largely restored in PCOS patients following assisted reproductive technology (ART) therapy. However, this recovery in menstrual cycles was not associated with any specific ART procedures. Using a PCOS mouse model, we demonstrated that elevated progesterone levels during pregnancy are responsible for normalizing estrous cyclicity. Elevated levels of progesterone induce granulosa cell apoptosis and deplete large follicles, which potentially contribute to ovarian function suppression during pregnancy. Mechanistic studies indicated that progesterone decreases FSH receptor (FSHR) expression in a Gata2-dependent manner. Interestingly, the capacity of granulosa cells to convert androgens into estrogens significantly increased after progesterone withdrawal, as evidenced by elevated Cyp19a1 expression in granulosa cells when stimulated with FSH. Additionally, we found that progesterone administration reduced the thickness of the uterine endometrium in PCOS mice. Our findings suggest that sustained high levels of progesterone during pregnancy can enhance ovarian reproductive endocrine capacity and improve endometrial function, thereby facilitating the recovery of postpartum menstrual cycles.
Keywords: polycystic ovary syndrome, menstrual cycle, progesterone, granulosa apoptosis
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