title: The signaling pathways by which the Fas/FasL system accelerates oocyte aging.
abstract: In spite of great efforts, the mechanisms for postovulatory oocyte aging are not fully understood. Although our previous work showed that the FasL/Fas signaling facilitated oocyte aging, the intra-oocyte signaling pathways are unknown. Furthermore, the mechanisms by which oxidative stress facilitates oocyte aging and the causal relationship between Ca2+ rises and caspase-3 activation and between the cell cycle and apoptosis during oocyte aging need detailed investigations. Our aim was to address these issues by studying the intra-oocyte signaling pathways for Fas/FasL to accelerate oocyte aging. The results indicated that sFasL released by cumulus cells activated Fas on the oocyte by increasing reactive oxygen species via activating NADPH oxidase. The activated Fas triggered Ca2+ release from the endoplasmic reticulum by activating phospholipase C-γ pathway and cytochrome c pathway. The cytoplasmic Ca2+ rises activated calcium/calmodulin-dependent protein kinase II (CaMKII) and caspase-3. While activated CaMKII increased oocyte susceptibility to activation by inactivating maturation-promoting factor (MPF) through cyclin B degradation, the activated caspase-3 facilitated further Ca2+releasing that activates more caspase-3 leading to oocyte fragmentation. Furthermore, caspase-3 activation and fragmentation were prevented in oocytes with a high MPF activity, suggesting that an oocyte must be in interphase to undergo apoptosis.
authors: College of Life Science, Northeast Agricultural University, Harbin, 150030, P. R. China.|Department of Assisted Reproduction Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 200011, P. R. China.
authors: Jiang
authors: J
authors: Zhu
authors: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai-an City 271018, P. R. China.
authors: Fei-Hu
authors: FH
authors: Lin
authors: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai-an City 271018, P. R. China.
authors: Jie
authors: J
authors: Zhang
authors: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai-an City 271018, P. R. China.
authors: Juan
authors: J
authors: Lin
authors: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai-an City 271018, P. R. China.
authors: Hong
authors: H
authors: Li
authors: College of Life Science, Northeast Agricultural University, Harbin, 150030, P. R. China.
authors: You-Wei
authors: YW
authors: Li
authors: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai-an City 271018, P. R. China.
authors: Xiu-Wen
authors: XW
authors: Tan
authors: College of Life Science, Northeast Agricultural University, Harbin, 150030, P. R. China.|College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai-an City 271018, P. R. China.
authors: Jing-He
authors: JH
authors: Tan
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D000090204:Mesothelin; D051379:Mice; D009865:Oocytes / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
chemical_list: D053222:Fas Ligand Protein; C000715528:Msln protein, mouse; D019014:fas Receptor; D000090204:Mesothelin
keywords: Fas/FasL; caspase-3; cytoplasmic Ca2+ rises; oocyte aging; phospholipase C