In Vitro Maturation of Fully Grown Mouse Antral Follicles in the Presence of 1 nM 2-Hydroxyestradiol Improves Oocytes’ Developmental Competence

Abstract

Cathecolestrogens are estradiol metabolites produced during folliculogenesis in the mammalian ovary. 2-Hydroxyestradiol (2-OHE 2) is one of the most abundant although its role remains unknown. The aim of this study is to investigate whether the presence of 2-OHE 2 during the germinal vesicle-to-metaphase II transition affects oocyte meiotic and preimplantation developmental competence. Mouse cumulus-oocyte complexes (COCs), isolated from fully grown antral follicles, were in vitro-matured (IVM) in the presence of 2-OHE 2 (0.1, 1, 10 or 100 nM) for 6 or 15 h; then, their meiotic and developmental competence was evaluated using a number of cytological quality markers. With the exception of the highest dose (100 nM), the addition of 2-OHE 2 to the IVM medium, did not alter, compared with untreated control, the frequency of oocytes that reached the MII stage. Instead, IVM in the presence of 1 nM 2-OHE 2 highly increased the rate of preimplantation development and blastocyst quality. To understand whether this positive effect could be attributed to the events occurring during meiosis resumption, we analysed a number of specific cytological quality markers of the asymmetric division, such as PB-I volume and position, presence and extension of the cortical F-actin cap, meiotic spindle shape and area, and microtubule organisation centre localisation. The results highlighted how the presence of 1 nM 2-OHE 2 significantly improved the overall cytological organisation required for a correct asymmetric division. Our results contribute a first step to acknowledge a potential role of this estradiol metabolite during the GVto-MII transition, contributing to the acquisition of oocytes developmental competence.

Exosomes Derived from Yak Follicular Fluid Increase 2-Hydroxyestradiol Secretion by Activating Autophagy in Cumulus Cells

“…Estrogens are signaling molecules converted from cholesterol to bioactive steroid hormones and this process is catalyzed by a series of different enzymes such as cytochrome P450 (CYP), the hydroxysteroid dehydrogenase (HSD) family, some lipid-binding proteins, and transporters [ 12 , 13 ]. 17β-estradiol mediates several cellular effects through its non-estrogenic metabolites (particularly 2-hydroxyestradiol and 4-hydroxyestradiol), which result after oxidative metabolism [ 14 ]. In this regard, the 17β-estradiol C2 hydroxylation leads to the formation of 2-OHE 2 , a metabolite that has no uterotropic activity, with a low affinity for estrogen receptors.…”