Ontogeny of adropin and its receptor expression during postnatal development and its pro-gonadal role in the ovary of pre-pubertal mouse

Abstract

Adropin, a highly conserved multifunctional peptide hormone, has a beneficial effect on the maintenance of gluco-lipid homeostasis, endothelial and cardiovascular functions. However, the expression and potential role of adropin in ovarian function are not fully elucidated. The present study aimed to investigate the expression of adropin and GPR19 in the mice ovary during various stages of postnatal development. This study also explored whether the treatment of adropin can modulate the timing of puberty, for which pre-pubertal mice were treated with adropin. The result showed the intense immunoreactivity of adropin in TICs, while GPR19 immunoreactivity was noted in GCs in infantile, pre-pubertal, and pubertal mice ovary. Also, adropin and GPR19 are highly expressed in the CL of the ovary of reproductively active mice. The fact that adropin expression in the ovary at different stages of postnatal development positively correlated with circulating progesterone and estradiol indicated that it has a role in the production of steroid hormones. Furthermore, the results of in vivo studies in pre-pubertal mice showed that adropin promotes early folliculogenesis by enhancing the proliferation (PCNA) of GCs of cortical ovarian follicles and promotes estradiol production by enhancing the expression of GPR19, StAR, CYP11A1 and aromatase proteins. Also, adropin treatment increases the Bax/Bcl2 ratio and expression of cleaved caspase-3 and ERα proteins, which may result in increased apoptosis of medullary follicles leading to the formation of a well-developed interstitium with interstitial glandular cells. Collectively, these findings indicate that adropin may be a factor that accelerates pubertal development in the ovary and could be utilized as a therapeutic approach for treating pubertal delay.