Adropin ameliorates reproductive dysfunctions in letrozole-induced PCOS mouse

Polycystic ovary syndrome (PCOS) is the most common cause of infertility in reproductive-age women, and its etiology and exact treatment are not yet established. Adropin is a unique hepatokine involved in maintaining energy homeostasis, and its level has been reported to decline in serum and follicular fluid of PCOS women. Thus, present study was designed to investigate the effect of adropin on hormonal and reproductive abnormalities in PCOS mice. PCOS was induced in adult mice by administering letrozole (6 mg/kg body weight) orally for 21 days. PCOS mice were subsequently treated with adropin (450 nmol/kg body weight) for 15 days. Adropin treatment drastically decreased serum testosterone by suppressing the ovarian expression of 17β-HSD in PCOS mice. It also improved the follicular proliferation and survival by enhancing the ovarian expression of PCNA and BCL2 and suppressing the BAX, cleaved caspase 3, and TUNEL-positive cells in PCOS mice. Most of the effects of adropin are comparable to metformin (current PCOS treatment). Notably, adropin shows more efficacy than metformin in treating reproductive abnormalities in PCOS mice, as evidenced by early regularization of cyclicity and enhanced ovarian expression of 3β-HSD and aromatase proteins. Thus, adropin may be an alternative therapeutic option for managing PCOS.