A possible role of estrogen receptors in primordial follicle activation in 3D culture model

Abstract

Increased primordial follicle activation induces immoderate depletion of ovarian reserve, premature ovarian insufficiency and first step for recruiting of growing follicle pools, so the regulation of primordial follicle activation is one of the crucial steps. Steroid hormones, especially estrogen, are known to play an important role in nest breakdown and subsequent follicle development. Although a relationship between the primordial follicle activation and E2 concentration is predicted in many studies, it is not well evaluated for dormancy or activation of primordial follicles. In this study, the anti-Müllerian hormone (Amh) knockout mice and in vitro culture model were employed to treat specific agonists and antagonists of the estrogen receptors and to compare the degree of activation. ESR1 and ESR2 were colocalized in oocyte cytoplasm in dormant and active follicle. The expression levels of the Esr1 mRNA and protein were significantly low in Amh KO ovary but not Esr2 and Gper1. Expectedly, the ratio of phosphate mTOR and Akt1 was high in the ovary of Amh null mice. Interestingly in wild type ovary, MPP, estrogen receptor alpha antagonist, treated group showed the highest degree of primordial activation and the dormant follicles were high in the PPT, estrogen receptor alpha agonist treated group. In Amh knockout ovary, MPP and PPT did not affect and instead G-1, GPR30 agonist, blocked activation. Based on the results, it is suggested that AMH may involved in E2 mediates estrogen receptor alpha to inhibit primordial follicle activation. And in the absence of AMH, estrogen receptor alpha does not function properly, GPR30 may work instead of it. Based on the results, it is suggest that Esr1 may have roles in follicle dormancy.