Abstract
Meiosis is the basis of sexual reproduction. In female mammals, meiosis of oocytes starts before birth and sustains at the dictyate stage of meiotic prophase I before gonadotropins-induced ovulation happens. Once meiosis gets started, the oocytes undergo the leptotene, zygotene, and pachytene stages, and then arrest at the dictyate stage. During each estrus cycle in mammals, or menstrual cycle in humans, a small portion of oocytes within preovulatory follicles may resume meiosis. It is crucial for females to supply high quality mature oocytes for sustaining fertility, which is generally achieved by fine-tuning oocyte meiotic arrest and resumption progression. Anything that disturbs the process may result in failure of oogenesis and seriously affect both the fertility and the health of females. Therefore, uncovering the regulatory network of oocyte meiosis progression illuminates not only how the foundations of mammalian reproduction are laid, but how mis-regulation of these steps result in infertility. In order to provide an overview of the recently uncovered cellular and molecular mechanism during oocyte maturation, especially epigenetic modification, the progress of the regulatory network of oocyte meiosis progression including meiosis arrest and meiosis resumption induced by gonadotropins is summarized. Then, advances in the epigenetic aspects, such as histone acetylation, phosphorylation, methylation, glycosylation, ubiquitination, and SUMOylation related to the quality of oocyte maturation are reviewed.
Highlights
Uncovering the signals involved in controlling the resumption of oocyte meiosis is a major issue in female reproductive biology
Applying natriuretic peptide precursor type C (NPPC) in cultured COCs contributes to preventing spontaneous oocyte maturation by increasing the cGMP levels in the cumulus granulosa cells (CGCs) (Zhang et al, 2010). These results suggest that cGMP produced in granulosa cells play a vital role in keeping the cyclic adenosine monophosphate (cAMP) level high in the oocyte, and that maintaining oocyte meiotic arrest requires coordination between granulosa cells and an oocyte within a follicle
The oocytes within antral follicles did not show precocious resumption of meiosis after deletion of the estrogen receptor or Cyp19α1 (Krege et al, 1998; Dupont et al, 2000; Kiyama and Wada-Kiyama, 2015), possibly implying that there are other pathways mediating NPPC/natriuretic peptide receptor 2 (NPR2) action. In line with this speculation, we have proved that the expression of the NPPC/NPR2 system in ovarian granulosa cells is up regulated by sex hormones, such as androgen and estrogen through respective hormone receptors (AR and endoplasmic reticulum (ER)) in physiological conditions, in polycystic ovary syndrome (PCOS) in mice ovaries, and in in vitro cultured granulosa cell lines (Liu et al, 2017; Reis and Honorato-Sampaio, 2018; Wang et al, 2018)
Summary
Uncovering the signals involved in controlling the resumption of oocyte meiosis is a major issue in female reproductive biology. Female germ cells enter and undergo the first meiotic progression during embryonic development, and arrest at the diplotene stage of prophase I before birth. Oocyte meiotic maturation is a complicated and vital process used to attain full competence required for the Meiosis Arrest and Resumption in Oocytes oocyte as well as early embryonic development. An oocyte arrested at meiotic prophase I contains a large nucleus covered by a nuclear envelope, which is known as the germinal vesicle (GV). With the arrival of LH surge, serial processes related to oocyte nuclear maturation, such as chromatin condensation and germinal vesicle breakdown (GVBD), occur in oocytes of fully grown follicles. The second meiosis starts and the oocyte (mature egg) arrests at metaphase II (MII) until fertilization. The oocyte accomplishes its meiosis progress only when fertilization happens
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