Towards a new understanding on the regulation of mammalian oocyte meiosis resumption

Abstract

Mammalian oocytes reach prophase of first meiosis around the time of birth, and remain at this stage for months or years, depending on the species. Only after puberty will the fully-grown oocytes begin to resume meiosis which is stimulated by gonadotropin surge. It has long been known that a high level of intra-oocyte cyclic adenosine 3',5'-monophosphate (cAMP) prevents oocyte meiosis resumption as indicated by germinal vesicle breakdown (GVBD). Recently, guanosine triphosphate-binding (G) protein-coupled receptors/G proteins/adenyl cyclase pathway endogenous to the oocyte as well as cAMP diffusion from the somatic compartment through gap junctions have been implicated in maintaining cAMP at levels that prevent oocytes from resuming meiosis. Another second messager molecule, guanosine 3',5'-cyclic monophosphate (cGMP), has also recently been found to play important roles in maintaining oocyte meiosis arrest. cGMP in the follicular somatic cells diffuses into the oocyte and causes an increase in oocyte cAMP, presumably by acting on phosphodiesterase 3 (PDE3). The cGMP level in the somatic compartment of the follicle decreases in response to luteinizing hormone (LH), and this change may be mediated through the epidermal growth factor (EGF)-like factors and specific cGMP-phosphodiesterase subtype activity. It is well known that gonadotropic stimulation of meiotic resumption depends on mitogen-activated protein kinase (MAPK) activation in the somatic compartment of the follicle; recent studies show that LH, through cAMP/protein kinase A (PKA) and protein kinase C (PKC) pathways, induces the synthesis of paracine factors such as EGF-like facors and meiosis activating sterol (MAS) to regulate oocyte GVBD via the MAPK pathway in follicle cells. A recent granulosa cell-specific knockout study has for the first time provided in vivo evidence for the important role of extracellular regulated kinase 1 and 2 (ERK1/2), two main forms of MAPK, and their downstream molecules in granulosa cells in oocyte meiosis resumption. Unresolved questions and future directions on research regarding signaling changes in follicle cells and oocytes as well their communication in response to the gonadotropin surge are addressed in this review.

Signaling pathways regulating FSH- and amphiregulin-induced meiotic resumption and cumulus cell expansion in the pig

“…The signaling in granulosa and cumulus cell, also modified by signals from the oocyte, removes the inhibitory influence of the follicle on the oocyte cell cycle and meiosis can resume (Sun et al 2009, Conti et al 2012.…”

Oxidative stress and ageing of the post-ovulatory oocyte

“…Upon release from the ovary, the prophase I oocyte undergoes a process of maturation involving resumption of meiosis, breakdown of the germinal vesicle and extrusion of the first polar body (reviewed by Sun et al (2009)). Following maturation, the oocyte once again enters meiotic arrest, now at metaphase II (MII).…”

Histone modifications during mammalian oocyte maturation: Dynamics, regulation and functions

“…When the microtubules become organized into a bipolar spindle and all chromosomes align at the spindle equator, the oocytes proceed to metaphase I (MI) stage, and subsequently extrude the first polar body, followed by entry into meiosis II and a second arrest at metaphase II (MII) stage. 15,16 Unlike mitosis, there are many events that specifically occur during meiotic progression, including successive M phases without an intervening DNA replication phase, pairing of homologous chromosomes, and asymmetric cell division, which raises the possibility that particular histone modification patterns may be presented during oocyte maturation and may play meiosis-specific roles. To date, histone modifications during oocyte maturation have been examined in diverse species and substantial results have been reported.…”