PMID- 10819779 OWN - NLM STAT- MEDLINE DCOM- 20000817 LR - 20220321 IS - 0006-3363 (Print) IS - 0006-3363 (Linking) VI - 62 IP - 6 DP - 2000 Jun TI - Involvement of mitochondria in oxidative stress-induced cell death in mouse zygotes. PG - 1745-53 AB - Accumulation of reactive oxygen species during aging leads to programmed cell death (PCD) in many cell types but has not been explored in mammalian fertilized eggs, in which mitochondria are "immature," in contrast to "mature" mitochondria in somatic cells. We characterized PCD in mouse zygotes induced by either intensive (1 mM for 1.5 h) or mild (200 microM for 15 min) hydrogen peroxide (H(2)O(2)) treatment. Shortly after intensive treatment, zygotes displayed PCD, typified by cell shrinkage, cytochrome c release from mitochondria, and caspase activation, then terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining in condensed pronuclei. On the other hand, after mild treatment, zygotes arrested developmentally and showed neither cytochrome c release nor caspase activation over 48 h; until 72 h, 46% zygotes exhibited TUNEL staining, and 88% of zygotes lost plasma membrane integrity. Interestingly, mild oxidative treatment induced a decline in mitochondrial membrane potential and disruption of the mitochondrial matrix. Taken together, these results suggest that oxidative stress caused by H(2)O(2) induces PCD in mouse zygotes and that mitochondria are involved in the early phase of oxidative stress-induced PCD. Furthermore, mitochondrial malfunction also may contribute to cell cycle arrest, followed by cell death, triggered by mild oxidative stress. FAU - Liu, L AU - Liu L AD - Department of Obstetrics & Gynaecology, Women & Infants Hospital, Brown University, Providence, Rhode Island 02905, USA. FAU - Trimarchi, J R AU - Trimarchi JR FAU - Keefe, D L AU - Keefe DL LA - eng GR - K081099/PHS HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Biol Reprod JT - Biology of reproduction JID - 0207224 RN - 0 (Cytochrome c Group) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 3.4.22.- (Caspases) SB - IM MH - Animals MH - *Apoptosis MH - Caspases/metabolism MH - Cell Nucleus/ultrastructure MH - Cytochrome c Group/metabolism MH - Enzyme Activation MH - Female MH - Hydrogen Peroxide/pharmacology MH - In Situ Nick-End Labeling MH - Membrane Potentials MH - Mice MH - Mitochondria/*physiology MH - *Oxidative Stress MH - Zygote/*ultrastructure EDAT- 2000/05/20 09:00 MHDA- 2000/08/19 11:00 CRDT- 2000/05/20 09:00 PHST- 2000/05/20 09:00 [pubmed] PHST- 2000/08/19 11:00 [medline] PHST- 2000/05/20 09:00 [entrez] AID - 10.1095/biolreprod62.6.1745 [doi] PST - ppublish SO - Biol Reprod. 2000 Jun;62(6):1745-53. doi: 10.1095/biolreprod62.6.1745.