Adropin effects on granulosa cell function and oocyte maturation in pigs

Abstract

Adropin, a peptide involved in energy homeostasis, acts via G protein-coupled receptor 19 (GPR19). This study examined the expression of adropin/GPR19 in porcine ovarian follicles and assessed the effects of adropin on granulosa cells (Gc) function and oocyte maturation in vitro. Levels of adropin/GPR19 were analyzed in porcine ovarian follicles and follicular fluid during the estrous cycle. Then, Gc isolated from medium-sized follicles were cultured with gonadotropins, steroids, or adropin (0.1–100 nM) to evaluate adropin/GPR19 expression, Gc function, and signaling pathways using pharmacological inhibitors. Additionally, the effect of adropin on oocyte maturation was assessed after in vitro maturation of cumulus-oocyte complexes from prepubertal pigs. We noted that adropin expression increased in the whole porcine ovarian follicle, while GPR19 decreased during the estrous cycle. Adropin protein expression and secretion to culture medium and GPR19 protein increased with gonadotropin and steroid treatment. Both proteins are localized to Gc and theca cells. Functionally, adropin reduced Gc viability via AKT signaling, inhibited proliferation and cell cycle progression via ERK1/2, suppressed estradiol secretion and CYP19A1 expression via PKA, increased progesterone secretion, cleaved caspase-3 expression and its activity, and inhibited autophagy-related markers. Adropinsimultaneously enhancing oocyte maturation, progesterone secretion, and lipid utilization in cumulus-oocyte complexes. These findings indicate that adropin may regulate porcine follicular development through its actions on Gc and oocytes.