title: Role of ataxia-telangiectasia mutated (ATM) in porcine oocyte in vitro maturation.
abstract: Ataxia-telangiectasia mutated (ATM) is critical for the DNA damage response, cell cycle checkpoints, and apoptosis. Significant effort has focused on elucidating the relationship between ATM and other nuclear signal transducers; however, little is known about the connection between ATM and oocyte meiotic maturation. We investigated the function of ATM in porcine oocytes. ATM was expressed at all stages of oocyte maturation and localized predominantly in the nucleus. Furthermore, the ATM-specific inhibitor KU-55933 blocked porcine oocyte maturation, reducing the percentages of oocytes that underwent germinal vesicle breakdown (GVBD) and first polar body extrusion. KU-55933 also decreased the expression of DNA damage-related genes (breast cancer 1, budding uninhibited by benzimidazoles 1, and P53) and reduced the mRNA and protein levels of AKT and other cell cycle-regulated genes that are predominantly expressed during G2/M phase, including bone morphogenetic protein 15, growth differentiation factor 9, cell division cycle protein 2, cyclinB1, and AKT. KU-55933 treatment decreased the developmental potential of blastocysts following parthenogenetic activation and increased the level of apoptosis. Together, these data suggested that ATM influenced the meiotic and cytoplasmic maturation of porcine oocytes, potentially by decreasing their sensitivity to DNA strand breaks, stimulating the AKT pathway, and/or altering the expression of other maternal genes.
authors.affiliation: Department of Animal Sciences, Chungbuk National University, Cheongju, Korea.
authors.forename: Zi-Li
authors.initials: ZL
authors.lastname: Lin
authors.affiliation: Department of Animal Sciences, Chungbuk National University, Cheongju, Korea.
authors.forename: Nam-Hyung
authors.initials: NH
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism*; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D048430:Cell Shape / Q000187:drug effects; D054885:Cumulus Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D059471:In Vitro Oocyte Maturation Techniques; D009025:Morpholines / Q000494:pharmacology; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology; D023121:RNA, Messenger, Stored / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D034421:Sus scrofa
chemical_list: C495818:2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one; D009025:Morpholines; D011753:Pyrones; D023121:RNA, Messenger, Stored; D064007:Ataxia Telangiectasia Mutated Proteins; D051057:Proto-Oncogene Proteins c-akt
keywords: ATM; in vitro maturation; porcine oocytes