The Phosphoinositide-Phospholipase C (PI-PLC) Pathway in the Mouse Oocyte

Abstract

As highlighted in this review, the phosphoinositide-phospholipase C pathway is strongly implicated in the control of mouse oocyte meiosis. The pathway becomes progressively functional as oocyte growth advances, and it appears to play a role in the G2/M transition when meiosis resumes, at least in the in vitro spontaneous model. Even if the inositol 1,4,5-trisphosphate receptors are present from the beginning, they function and release Ca2+ when the follicular antrum appears. Phospholipase C beta1 (PLC beta 1) is first exclusively localized to the nucleus and then migrates to the cytoplasm when the oocyte is fully grown. During oocyte maturation PLC beta 1 is active in the cytoplasm before it migrates and becomes active in the nucleus just prior to germinal vesicle breakdown. Because a similar circuit is observed for protein kinase C alpha (PKC alpha), PKC beta 1, PKC beta 2, and active mitogen-activated protein kinase, it is tempting to envisage that a feedback loop occurs between these pathways as demonstrated in other cell types. The chronology of these molecular movements into the oocyte reveals the particular and important role of the nucleus phosphoinositide cycle during oocyte meiosis. It appears also that this chronology is crucial and that defects leading to an inappropriate intracellular localization can have dramatic consequences. Such anomalies can prevent the production of competent oocytes and lead to fertility problems.

Copy Number Variants in Premature Ovarian Failure and Ovarian Dysgenesis

“…The phosphoinositide-phospholipase C pathway plays a role in the G2/M transition in mouse oocytes when meiosis resumes [Lefevre et al, 2007]. Therefore, it can be expected that an impaired function of PLCB1 leads to reduced fertility.…”

Protein kinases and ovarian functions

“…Occurrence of members of MAPK (Meidan et al, 2005), PKC (Gadsby et al, 2006), and PKA (Dupont et al, 2008) families was demonstrated in ovarian Corpus luteum. Representatives of PKA, MAPK, PI3K, Akt, CaMK, PKC, AK, Janus kinases (JNKs), and myosin light chain kinase (MLCK) are found in oocytes, whilst their expression and localization depends on stage of oocyte maturation (Sirotkin et al, 2000a,c;Kimura et al, 2007;Lefèvre et al, 2007;Ducibella and Fissore, 2008;Mermillod et al, 2008).…”

“…7). Influence of FSH on ovarian members of PKA, MAPK, CDK, PI3K, Akt, CaMK, PKC and other PKs or their mRNAs (Gadsby et al, 2006;Hunzicker-Dunn and Maizels, 2006;Dupont et al, 2008;Lefèvre et al, 2007) has been documented. There are reports on the action of GH on ovarian PKA and MAPK Sirotkin, 2005; Fig.…”

“…Involvement of PI3K and CDK in promotion of oocyte growth (McLaughlin and McIver, 2009) and of PKA, PKG, MAPKs, PI3K, CDKs, TKs including EGFR, PKC, CaMK, and MLCK in control oocyte maturation and cytokinesis (Makarevich et al, 1997;Fan and Sun, 2004;Masciarelli et al, 2004;Brunet and Maro, 2005;Dekel, 2005;Motola et al, 2006;Kimura et al, 2007;Lefèvre et al, 2007;Ducibella and Fissore, 2008;Mermillod et al, 2008) have been documented. Oocytes in the ovarian follicles are usually arrested at the first meiotic prophase, held in meiotic arrest by the surrounding follicle cells until a surge of gonadotropins from the pituitary or disconnection of oocyte from surrounding follicular cells stimulates the immature oocyte to resume meiosis.…”

The nucleolus of the maternal gamete is essential for life

“…At the same time, the rate of transcription is initially very high but is finally arrested, (7) and nuclear calcium signaling progressively functions. (8) Proteins migrate from the cytoplasm to the nucleus, or vice versa, depending on oocyte maturity; (9,10) indeed, NSN GV-oocyte nucleoli display a different protein profile to SN GV-oocyte nucleoli. (11) The nucleolar protein, SURF6, detected in NSN but not SN GV oocytes, appears to be essential for embryo development and knock-down of SURF6 mRNA results in embryo developmental arrest.…”