Prophase I arrest and progression to metaphase I in mouse oocytes: comparison of resumption of meiosis and recovery from G2-arrest in somatic cells

Abstract

Mammalian oocytes are arrested at prophase I until puberty when luteinizing hormone (LH) induces resumption of meiosis of follicle-enclosed oocytes. Resumption of meiosis is tightly coupled with regulating cyclin-dependent kinase 1 (CDK1) activity. Prophase I arrest depends on inhibitory phosphorylation of CDK1 and anaphase-promoting complex-(APC-CDH1)-mediated regulation of cyclin B levels. Prophase I arrest is maintained by endogenously produced cyclic adenosine monophosphate (cAMP), which activates protein kinase A (PKA) that in turn phosphorylates (and activates) the nuclear kinase WEE2. In addition, PKA-mediated phosphorylation of the phosphatase CDC25B results in its cytoplasmic retention. The combined effect maintains low levels of CDK1 activity that are not sufficient to initiate resumption of meiosis. LH triggers synthesis of epidermal growth factor-like factors in mural granulosa cells and leads to reduced cGMP transfer from cumulus cells to oocytes via gap junctions that couple the two cell types. cGMP inhibits oocyte phosphodiesterase 3A (PDE3A) and a decline in oocyte cGMP results in increased PDE3A activity. The ensuing decrease in oocyte cAMP triggers maturation by alleviating the aforementioned phosphorylations of WEE2 and CDC25B. As a direct consequence CDC25B translocates into the nucleus. The resulting activation of CDK1 also promotes extrusion of WEE2 from the nucleus thereby providing a positive amplification mechanism for CDK1 activation. Other kinases, e.g. protein kinase B, Aurora kinase A and polo-like kinase 1, also participate in resumption of meiosis. Mechanisms governing meiotic prophase I arrest and resumption of meiosis share common features with DNA damage-induced mitotic G2-checkpoint arrest and checkpoint recovery, respectively. These common features include CDC14B-dependent activation of APC-CDH1 in prophase I arrested oocytes or G2-arrested somatic cells, and CDC25B-dependent cell cycle resumption in both oocytes and somatic cells.

Sirt2‐BubR1 acetylation pathway mediates the effects of advanced maternal age on oocyte quality

“…Anaphase I usually occurs when all chromosome bivalents have established stable kinetochore–microtubule (K‐MT) interactions. Then, oocytes enter directly into meiosis II without an intervening S‐phase and arrest at metaphase II (MII) stage waiting for fertilization (Solc, Schultz, & Motlik, 2010; Watanabe, 2012). Unfortunately, the meiotic divisions in oocytes are highly error prone (Fragouli et al., 2011; Kuliev, Zlatopolsky, Kirillova, Spivakova, & Cieslak Janzen, 2011).…”

Regulation of sheep oocyte maturation using cAMP modulators

“…Cyclic guanosine monophosphate (cGMP) diffuses from granulosa cells to the oocyte and inhibits cAMP degradation by inhibiting PDE3A [5,6]. In rodents, elevated cAMP concentrations activate protein kinase-A (PKA), followed by complex inhibitory mechanisms involving CDK1 -cyclin B kinase proteins suppressing activation of maturation promoting factor (MPF) and preventing meiosis [7][8][9]. In vivo, the pre-ovulatory surge of LH decreases cGMP concentrations in granulosa cells as well as oocytes [5,6]; the subsequent activation of PDE3A resulted in degradation of cAMP, activation of MPF, and resumption of meiosis (review; Conti et.…”

The DNA Damage Response in Mammalian Oocytes.

“…The mechanisms regulating meiotic prophase arrest and resumption of meiosis resemble the establishment of the somatic cell G2 DDC and checkpoint recovery, respectively (Figures 2 and 3; Bassermann et al, 2008;Solc et al, 2010). The major common element in both systems is the alteration of cyclin B-CDK1 activity, predominantly through the action of CDK1 activators and inhibitors (Bassermann et al, 2008;Solc et al, 2010).…”

“…The major common element in both systems is the alteration of cyclin B-CDK1 activity, predominantly through the action of CDK1 activators and inhibitors (Bassermann et al, 2008;Solc et al, 2010). FIGURE 2 | Schematic representation of the major steps of the G2 DNA damage checkpoint.…”

“…(LH), during the estrus cycle, cAMP levels drop and PKA becomes inactive allowing CDC25B activation and the subsequent cyclin B-CDK1 activation leading to entry into the first meiotic M-phase (MI; Lincoln et al, 2002;Marangos and Carroll, 2004;Solc et al, 2010). Most of the information we possess regarding the mammalian oocyte DDR involves prophase arrest.…”