Function and molecular mechanism of mitogen-activated protein kinase (MAPK) in regulating oocyte meiotic maturation and ovulation / 生理学报

ABSTRACT

The mitogen-activated protein kinase (MAPK) signaling pathway is a highly conserved signal transduction pathway from yeast to human species, and is widely distributed in various eukaryotic cells. In almost all of the species studied over the past three decades, this signaling pathway plays a crucial role in the development of female germ cells and meiotic maturation. Especially in a variety of mammalian species including primates, rodents, and domestic animals, the MAPK signaling pathway is activated during the resumption of first oocyte meiosis and plays an indispensable role in meiotic spindle assembly and cell cycle progression. In granulosa cells of fully grown ovarian follicles, the MAPK pathway also mediates the physiological action of gonadotropins, including cumulus expansion, ovulation, and corpus luteum formation. Although the MAPK signaling pathway plays a wide range of physiological functions during the female reproduction process, and these functions are highly conserved in evolution, their underlying mechanisms, especially their direct and physiological target molecules, have not been sufficiently studied for a long time. In recent years, based on some new gene-editing mouse models and theoretical findings, as well as the wide application of various omics techniques, it has been further revealed that MAPK directly phosphorylates and activates the RNA binding protein cytoplasmic polyadenylation element-binding protein-1 (CPEB1), promoting poly(A) tail extension of maternal mRNA to regulate protein translation during meiotic recovery. These findings not only constitute the current basic mechanism of mammalian oocyte maturation and ovulation, but also provide useful research ideas for other related research in this field. In this review, we summarize the research findings in our laboratory and from other groups regarding the role of MAPK cascade in regulating oocyte maturation and ovulation. We also discuss the latest research progress on MAPK regulation of mRNA translation and degradation by directly activating the translation initiation complex and mRNA poly(A) polymerase by phosphorylation in the granulosa cells.