Cyclooxygenase-2-derived Prostaglandin E2 Directs Oocyte Maturation by Differentially Influencing Multiple Signaling Pathways

Department of Cell and Developmental Biology, Vanderbilt University, Нашвилл, Michigan, United States
Journal of Biological Chemistry (Impact Factor: 4.57). 01/2007; 281(48):37117-29. DOI: 10.1074/jbc.M608202200
Source: PubMed


The process of oocyte maturation, which impacts ovulation and fertilization, is complex and requires an integration of the endocrine, paracrine, juxtacrine, and autocrine signaling pathways. This process involves an intimate interaction between the oocyte and encircling cumulus cells within a follicle, a unique venue for somatic and germ cell communication. Cumulus cell expansion and resumption of meiosis with germinal vesicle breakdown are major events in oocyte maturation. Cyclooxygenase-2 (COX-2)-derived prostaglandin E(2) (PGE(2)) is a known critical mediator of oocyte maturation, but the diverse function of this lipid mediator in oocyte maturation, ovulation, and fertilization has not been fully appreciated. We show here that gonadotropins in coordination with PGE(2) signaling via its cell surface G-protein-coupled EP2 and EP4 receptor subtypes direct cumulus cell expansion and survival and oocyte meiotic maturation by differentially impacting cAMP-dependent protein kinase, MAPK, NF-kappaB, and phosphatidylinositol 3-kinase/Akt pathways. This study is unique in the sense that it provides evidence for new site- and event-specific involvement of these signaling pathways under the influence of COX-2-derived PGE(2) during the critical stages of this somatic-germ cell interaction, an absolute requirement for oocyte maturation.

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Available from: Haibin Wang, Aug 18, 2015
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    • "Ptgs2 expression in cumulus cells is rate limiting for prostaglandin E2 (PGE2) production which is a critical mediator of cumulus expansion (Eppig 1981; Hizaki et al. 1999). Ptgs2−/− mice failed to show any cumulus expansion and also exhibited severe defects in meiotic progression during the preovulatory period (Lim et al. 1997; Davis et al. 1999; Takahashi et al. 2006). Similar defects in cumulus expansion were observed in the bovine system upon partial inhibition of PTGS2 activity during in-vitro oocyte maturation. "
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    • "Therefore, cumulus expansion in monkey may be regulated by both EP2 and EP3-9 by responding to elevated follicular PGE2 with increased cAMP. In the mouse, Ep2 mRNA was highly expressed in cumulus cells just before ovulation (Segi et al. 2003, Takahashi et al. 2006), consistent with the concept that cumulus expansion is regulated by this Gαs-coupled receptor. Mice lacking Ep2 expression have a severe deficiency in cumulus expansion, partially via reduction of tumor necrosis factor α-induced protein 6 (Tnfaip6) selectively in cumulus cells of preovulatory follicles (Hizaki et al. 1999, Ochsner et al. 2003). "
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