title: Notch pathway regulates female germ cell meiosis progression and early oogenesis events in fetal mouse.
abstract: A critical process of early oogenesis is the entry of mitotic oogonia into meiosis, a cell cycle switch regulated by a complex gene regulatory network. Although Notch pathway is involved in numerous important aspects of oogenesis in invertebrate species, whether it plays roles in early oogenesis events in mammals is unknown. Therefore, the rationale of the present study was to investigate the roles of Notch signaling in crucial processes of early oogenesis, such as meiosis entry and early oocyte growth. Notch receptors and ligands were localized in mouse embryonic female gonads and 2 Notch inhibitors, namely DAPT and L-685,458, were used to attenuate its signaling in an in vitro culture system of ovarian tissues from 12.5 days post coitum (dpc) fetus. The results demonstrated that the expression of Stra8, a master gene for germ cell meiosis, and its stimulation by retinoic acid (RA) were reduced after suppression of Notch signaling, and the other meiotic genes, Dazl, Dmc1, and Rec8, were abolished or markedly decreased. Furthermore, RNAi of Notch1 also markedly inhibited the expression of Stra8 and SCP3 in cultured female germ cells. The increased methylation status of CpG islands within the Stra8 promoter of the oocytes was observed in the presence of DAPT, indicating that Notch signaling is probably necessary for maintaining the epigenetic state of this gene in a way suitable for RA stimulation. Furthermore, in the presence of Notch inhibitors, progression of oocytes through meiosis I was markedly delayed. At later culture periods, the rate of oocyte growth was decreased, which impaired subsequent primordial follicle assembly in cultured ovarian tissues. Taken together, these results suggested new roles of the Notch signaling pathway in female germ cell meiosis progression and early oogenesis events in mammals.
authors.affiliation: Laboratory of Germ Cell Biology; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong; College of Animal Science and Technology; Qingdao Agricultural University; Qingdao, China.
authors.forename: Yan-Min
authors.initials: YM
authors.lastname: Feng
authors.affiliation: Laboratory of Germ Cell Biology; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong; College of Animal Science and Technology; Qingdao Agricultural University; Qingdao, China.
authors.forename: Gui-Jin
authors.initials: GJ
authors.lastname: Liang
authors.affiliation: Department of Animal and Poultry Science; University of Guelph; Guelph, Ontario, Canada.
authors.forename: Bo
authors.initials: B
authors.lastname: Pan
authors.affiliation: Laboratory of Germ Cell Biology; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong; College of Animal Science and Technology; Qingdao Agricultural University; Qingdao, China.
authors.forename: Xun-Si
authors.initials: XS
authors.lastname: Qin
authors.affiliation: College of Biological and Pharmaceutical Engineering; Wuhan Polytechnic University; Wuhan, China.
authors.forename: Xi-Feng
authors.initials: XF
authors.lastname: Zhang
authors.affiliation: Laboratory of Germ Cell Biology; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong; College of Animal Science and Technology; Qingdao Agricultural University; Qingdao, China.
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Laboratory of Germ Cell Biology; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong; College of Animal Science and Technology; Qingdao Agricultural University; Qingdao, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.affiliation: Laboratory of Germ Cell Biology; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong; College of Animal Science and Technology; Qingdao Agricultural University; Qingdao, China.
authors.forename: Shun-Feng
authors.initials: SF
authors.lastname: Cheng
authors.affiliation: Department of Biomedicine and Prevention; University of Rome "Tor Vergata"; Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: De Felici
authors.affiliation: Laboratory of Germ Cell Biology; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong; College of Animal Science and Technology; Qingdao Agricultural University; Qingdao, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002219:Carbamates / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000166:cytology; D008540:Meiosis; D008745:Methylation; D051379:Mice; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009866:Oogenesis; D011401:Promoter Regions, Genetic; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002219:Carbamates; D004151:Dipeptides; C410009:L 685458; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; C102019:Stra8 protein, mouse; D014212:Tretinoin
keywords: Stra8; meiosis; mouse; notch; oogenesis