Adropin in polycystic ovarian syndrome: expression and impact on human granulosa cells function

Abstract

Adropin is a new protein that regulates energy homeostasis. The serum and follicular fluid (FF) levels of adropin are decreased in women with polycystic ovarian syndrome (PCOS); however, its role in ovarian function is unknown. The aims were to determine the expression of adropin and its receptor G protein-coupled receptor 19 (GPR19) in human granulosa cells (GC), its immunolocalization and its in vitro effects on GC function. Blood plasma, FF and GC samples were obtained from normal weight, obese and diagnosed with or without PCOS women (n=8). The in vitro effects of adropin on GC proliferation, apoptosis, cell cycle progression, steroidogenesis were analyzed. The results revealed that adropin plasma concentration was decreased in obese patients, with a similar reduction observed in obese patients with PCOS, while GPR19 expression was decreased in the GC of obese and PCOS women, as well as in obese PCOS patients. We noted that in all investigated patients groups adropin reduced GC proliferation and cell cycle progression, negatively influenced steroidogenesis enzyme levels and promoted apoptosis. Such disruptions in GC function are likely to impair ovarian follicular maturation and contribute to the subfertility commonly observed in PCOS. Such alterations may ultimately affect oocyte competence and ovarian responsiveness, parameters that are clinically relevant for in vitro fertilization outcomes. Our findings suggest that adropin may act as a novel regulator of ovarian function and could contribute to the pathophysiology of PCOS, highlighting its potential clinical value as a marker of altered ovarian follicular function in affected women.