(4)中枢神経関連生理活性物質の卵成熟・胚発育・着床への影響(<特集>第61回学術講演会シンポジウム2「中枢神経関連生理活性物質の生殖機能へのかかわり」)

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In mammals, rupture of ovarian follicles and final maturation of oocytes occur in response to stimulation by pituitary derived luteinizing hormones (LH) that act on the somatic granulosa and theca cells surrounding the oocyte. Because LH interacts only with ovarian somatic cells, its potential regulation of oocyte functions is presumably mediated by local paracrine factors. Shortly after stimulation by the preovulatory surge of LH, oocytes arrested at the late prophase resume meiosis characterized by germinal vesicle (nuclear envelope) breakdown (GVBD), chromosome condensation, and extrusion of the first polar body in preparation for fertilization and early embryonic development. In addition to nuclear maturation exemplified by GVBD and extrusion of the first polar body to complete the first meiotic division, oocytes also undergo cytoplasmic maturation characterized by cytoplasmic changes essential for monospermic fertilization, processing of the sperm, and preparation for development to preimplantation embryos. Although the spermatozoon provides an essential element for embryo generation, the developmental fate of the embryo is principally dictated by the oocyte. Accumulating evidence indicates that a number of growth factors and cytokines act as paracrine and/or autocrine factors during early embryo development, and implantation, and subsequent placental/fetal development. In addition, developing early embryos produce growth factors that act in an autocrine manner to regulate their own growth and differentiation, or to serve as paracrine factors by regulating endometrial receptivity for blastocyst implantation. Here, we show novel neuro-associated physiologically active substances that regulate oocyte maturation, preimplantation embryo development and implantation. We performed DNA microarray analyses using ovaries following gonadotropin stimulation and identified candidate ligand-receptor pairs potentially involved in the process of oocyte maturation. Among ovarian genes, we selected the candidates of neuro-associated physiologically active substances based on the increased expression levels by the preovulatory LH surge and localization of ligands and receptors in ovarian somatic cells and oocytes or cumulus-oocyte complexes, respectively. Using in vitro and in vivo studies for oocyte nuclear and cytoplasmic maturation, we determined novel ovarian paracrine factors for induction of oocyte maturation. We also found novel paracrine factors that stimulate early embryonic development, implantation and placental development based on the localization of ligand-receptor pairs in reproductive tracts, preimplantation embryos and placentas. In this meeting, I have shown the precise roles of brain derived neurotrophic factor on behalf of the novel factors, and summarized the actions of glial cell line-derived neurotrophic factor and leptin in oocyte maturation, embryo development, implantation and placental development. Our findings contribute not only on the insight into mechanisms of early reproduction, but also on future clinical applications for in vitro maturation of oocytes, facilitation of implantation, stimulation of placental/fetal development in intra-uterine growth retardation, treatment of ectopic pregnancy and safe contraception using the neuro-associated physiologically active substances or their specific inhibitors.
社団法人日本産科婦人科学会の論文
2009-10-01

著者

河村和弘
秋田大学大学院医学系研究科医学専攻機能展開医学系産婦人科学講座

(4)中枢神経関連生理活性物質の卵成熟・胚発育・着床への影響(<特集>第61回学術講演会シンポジウム2「中枢神経関連生理活性物質の生殖機能へのかかわり」)

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