Berberine improves ovulation and endometrial receptivity in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a clinical syndrome with reproductive and endocrine disorders. Berberine is a monomer from Chinese herbs such as Coptis chinensis, whose effect on improving ovulation and endometrial receptivity of PCOS is uncertain. To evaluate the effect of berberine on improving PCOS and explore the mechanism. The rat model of PCOS was induced by intraperitoneal injection of testosterone propionate. Then they was divided into model (Mod) group, low-dose of berberine (BL) group, high-dose of berberine (BH) group and metformin (Met) group as well as a control (Con) group was established. Ovary morphology, hormone level, glucolipid metabolism were measured. UID-mRNA-seq of ovary tissue was conducted to seek the mechanism of berberine on improving ovulation. Three biomarkers of endometrial receptivity were also examined in endometrium by immunohistochemistry. The number of cystic follicles was increased while the number of corpus luteum was decreased in the rats of Mod group. These changes could be reversed by high-dose of berberine intervention. Berberine could also decrease the levels of serum luteinizing hormone (LH) and total cholesterol (TC) in PCOS rats. Meanwhile, berberine improved the impairment of abnormal oral glucose tolerance without affecting fasting insulin level and Homeostasis model assessment-insulin resistance (HOMA-IR). Luteinizing hormone/ choriogonadotropin receptor (LHCGR) and cytochrome P450 Family 19 Subfamily A Member 1 (CYP19A1) were focused via RNA-seq of ovary. Protein expression in ovary and mRNA expression in granulosa cell of LHCGR and CYP19A1 were decreased in Mod group and rescued by the intervention of berberine. A decrease of endometrial thickness and an increase of integrin αvβ3 and lysophosphatidic acid receptor 3 (LPAR3) protein expression were observed in Mod group, which could be also reversed by berberbine. Berberine could improve ovulation in PCOS and the mechanism might be associated with up-regulating LHCGR and CYP19A1. Berberine could also improve endometrial receptivity through down-regualting αvβ3 and LPAR3.