title: Completion of Meiosis I of preovulatory oocytes and facilitation of preimplantation embryo development by glial cell line-derived neurotrophic factor.
abstract: Optimal maturation of oocytes and successful development of preimplantation embryos is essential for reproduction. We performed DNA microarray analyses of ovarian transcripts and identified glial cell line-derived neurotrophic factor (GDNF) secreted by cumulus, granulosa, and theca cells as an ovarian factor stimulated by the preovulatory LH/hCG surge. Treatment of cumulus-oocyte complexes with GDNF enhanced first polar body extrusion with increase in cyclin B1 synthesis and the GDNF actions are likely mediated by its receptor GDNF family receptor-alpha1 (GFRA1) and a co-receptor ret proto-oncogene (Ret), both expressed in oocytes. However, treatment with GDNF did not affect germinal vesicle breakdown and cytoplasmic maturation of oocytes. During the preimplantation stages, GDNF was expressed in pregnant oviducts and uteri, whereas GFRA1 and Ret were expressed in embryos throughout early development with an increase after the early blastocyst stage. In blastocysts, both GDNF and GFRA1 were exclusively localized in trophectoderm cells, whereas Ret was detected in both cell lineages. Treatment with GDNF promoted the development of two-cell-stage embryos into blastocysts showing increased cell proliferation and decreased apoptosis mainly in trophectoderm cells. Our findings suggest potential paracrine roles of GDNF in the promotion of completion of meiosis I and the development of early embryos.
authors.affiliation: Department of Obstetrics and Gynecology, Akita University School of Medicine, Akita 010-8543, Japan. kawamura@yf7.so-net.ne.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kawamura
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Ye
authors.forename: Nanami
authors.initials: N
authors.lastname: Kawamura
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.forename: Peter
authors.initials: P
authors.lastname: Groenen
authors.forename: Maarten Sollewijn
authors.initials: MS
authors.lastname: Gelpke
authors.forename: Rami
authors.initials: R
authors.lastname: Rauch
authors.forename: Aaron J W
authors.initials: AJ
authors.lastname: Hsueh
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054885:Cumulus Cells / Q000166:cytology; D004622:Embryo, Mammalian / Q000378:metabolism*; D047108:Embryonic Development; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D006080:Ovarian Follicle / Q000166:cytology; D010053:Ovary / Q000166:cytology; D010057:Oviducts / Q000378:metabolism; D011247:Pregnancy; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013223:Statistics as Topic; D014599:Uterus / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins