title: 5-Azacytidine induces early stage apoptosis and promotes in vitro maturation by changing chromosomal construction in murine oocytes.
abstract: As an anticancer drug, 5-azacytidine (5-AzaC) has been widely used to treat various cancers. To investigate the effect of 5-AzaC on mouse oocytes cultured in vitro, we have performed morphological and molecular biology studies to examine the behavior of chromosomes and oocyte development. In 5-AzaC-treated oocytes, chromosomes were decondensed and unstable. The mRNA levels of Caspase3, Caspase8, and Caspase9 increased with the occurrence of early stage apoptosis in oocytes following 5-AzaC treatment. Furthermore, the mRNA levels of Gdf9 and Bmp15 also increased with the corresponding morphological changes in 5-AzaC-treated oocytes. In conclusion, 5-AzaC not only induced early apoptosis through both extrinsic and intrinsic pathways, but also had a positive effect on the developmental competence of mouse oocytes during in vitro maturation. These effects may be due to changes in chromosomal construction induced by DNA hypomethylation.
authors: State Key Laboratory of Low-Dimensional Quantum Physics, Department of Physics, Tsinghua University, Beijing 100084, People's Republic of China. jldxzfy004950@126.com
authors: F Y
authors: FY
authors: Zhao
authors: C P
authors: CP
authors: Shao
authors: Y
authors: Y
authors: Li
authors: W Y
authors: WY
authors: Ma
authors: N
authors: N
authors: Tian
authors: J H
authors: JH
authors: Zheng
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000633:toxicity*; D020169:Caspases / Q000235:genetics; D048708:Cell Growth Processes / Q000187:drug effects; D002478:Cells, Cultured; D002875:Chromosomes / Q000378:metabolism; D005260:Female; D051379:Mice; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D020169:Caspases; D001374:Azacitidine