Estrogen receptors in granulosa cells govern meiotic resumption of pre-ovulatory oocytes in mammals

Abstract

In mammals, oocytes are arrested at the diplotene stage of meiosis I until the pre-ovulatory luteinizing hormone (LH) surge triggers meiotic resumption through the signals in follicular granulosa cells. In this study, we show that the estradiol (E2)-estrogen receptors (ERs) system in follicular granulosa cells has a dominant role in controlling oocyte meiotic resumption in mammals. We found that the expression of ERs was controlled by gonadotropins under physiological conditions. E2-ERs system was functional in maintaining oocyte meiotic arrest by regulating the expression of natriuretic peptide C and natriuretic peptide receptor 2 (NPPC/NPR2), which was achieved through binding to the promoter regions of Nppc and Npr2 genes directly. In ER knockout mice, meiotic arrest was not sustained by E2 in most cumulus–oocyte complexes in vitro and meiosis resumed precociously in pre-ovulatory follicles in vivo. In human granulosa cells, similar conclusions are reached that ER levels were controlled by gonadotropins and E2-ERs regulated the expression of NPPC/NPR2 levels. In addition, our results revealed that the different regulating patterns of follicle-stimulating hormone and LH on ER levels in vivo versus in vitro determined their distinct actions on oocyte maturation. Taken together, these findings suggest a critical role of E2-ERs system during oocyte meiotic progression and may propose a novel approach for oocyte in vitro maturation treatment in clinical practice.

Maturation promoting factor destabilization mediates human chorionic gonadotropin induced meiotic resumption in rat oocytes

“…The successful completion of meiotic competency determines oocyte quality, which is a primary requirement for successful fertilization, early embryonic development and reproductive outcome (Liu et al . ).…”

Exposure to cigarette smoke via respiratory system may induce abnormal alterations of reproductive organs in female diabetic rats

“…Our study also showed that CS increased ERα in both the uterus and ovary. In mammals, ERα plays a crucial role in the physiological processes of female reproductive organs with ER subtypes predominating in fallopian tubes and the uterus . Additionally, altered occurrence of ERα may be related to the morphology and functional integrity of reproductive organs .…”

Technologies for the Production of Fertilizable Mammalian Oocytes

“…Since meiotic arrest is ensured by a high intraoocyte concentration of cyclic adenosine monophosphate (cAMP), the cGMP-dependent inhibition of phosphodiesterase 3A (PDE3A) activity in the oocyte maintains the GV stage. Conversely, preovulatory LH surge downregulates ER and, as a consequence, the decrease of NPPC and NPR2 levels triggers oocyte meiotic resumption [62]. In addition, CC-dependent secretion of a hyaluronan-rich matrix facilitates the uncoupling of the cumulus-oocyte contacts (cumulus expansion).…”