Biochanin-A attenuates DHEA-induced polycystic ovary syndrome via upregulation of GDF9 and BMP15 signaling in vivo

Phytoestrogens can act as natural estrogens owing to their structural similarity to human estrogens. Biochanin-A (BCA) is a well-studied phytoestrogen with a wide variety of pharmacological activities, whereas not reported in the most frequently encountered endocrinopathy called polycystic ovary syndrome (PCOS) in women.This study aimed to investigate the therapeutic effect of BCA on dehydroepiandrosterone (DHEA) induced PCOS in mice.Thirty-six female C57BL6/J mice were divided into six groups: sesame oil, DHEA-induced PCOS, DHEA + BCA (10 mg/kg/day), DHEA + BCA (20 mg/kg/day), DHEA + BCA (40 mg/kg/day), and metformin (50 mg/kg/day).The results showed a decrease in obesity, elevated lipid parameters, restoration of hormonal imbalances (testosterone, progesterone, estradiol, adiponectin, insulin, luteinizing hormone, and follicle-stimulating hormone), estrus irregular cyclicity, and pathological changes in the ovary, fat pad, and liver.In conclusion, BCA supplementation inhibited the over secretion of inflammatory cytokines (TNF-α, IL-6, and IL-1β) and upregulated TGFβ superfamily markers such as GDF9, BMP15, TGFβR1, and BMPR2 in the ovarian milieu of PCOS mice. Furthermore, BCA reversed insulin resistance by increasing circulating adiponectin levels through a negative correlation with insulin levels. Our results indicate that BCA attenuated DHEA-induced PCOS ovarian derangements, which could be mediated by the TGFβ superfamily signaling pathway via GDF9 and BMP15 and associated receptors as first evidenced in this study.