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Title: Alterations in mitochondrial morphology are associated with hyperthermia-induced apoptosis in early postimplantation mouse embryos.

Authors: Kim, Won-Kyu; Mirkes, Philip E

Published In Birth Defects Res A Clin Mol Teratol, (2003 Nov)

Abstract: BACKGROUND: Previously, we showed that teratogens such as hyperthermia activate the mitochondrial apoptotic pathway in day nine mouse embryos. Activation of this pathway involves an initial release of cytochrome c from intermembranous spaces of the mitochondria into the cytoplasm. Cytoplasmic cytochrome c then activates a caspase cascade resulting in the orderly demise of the cell. In addition, we showed that teratogens activate the mitochondrial pathway in cells of the neuroepithelium, but not the heart. METHODS: To further investigate the role of the mitochondrion in teratogen-induced apoptosis, we used transmission electron microscopy (TEM) to compare mitochondrial morphology in cells of the neuroepithelium and heart of control and hyperthermia-treated embryos. Because we know that the apoptotic pathway is activated some time during the first 5 hr after teratogen exposure is initiated, we assessed mitochondrial morphology at 1, 2.5, and 5 hr after day nine mouse embryos were exposed to hyperthermia (43 degrees C, 15 min). RESULTS: In neuroepithelial cells of the prosencephalon, abnormally-shaped mitochondria were observed at the 1 hr time point and thereafter, whereas loss of cristae and shrunken mitochondria were noted at the 5 hr time point. In contrast, no obvious changes in mitochondria of heart cells were observed at any of the time points monitored. CONCLUSIONS: These results indicate that teratogen-induced cell death in neuroepithelial cells is temporally correlated with alterations in mitochondrial morphology, whereas the absence of cell death in the heart is correlated with a corresponding lack of change in mitochondrial morphology. Birth Defects Research (Part A), 2003.

PubMed ID: 14745931 Exiting the NIEHS site

MeSH Terms: Animals; Apoptosis; Cell Death; Cytochromes c/metabolism; Cytoplasm/metabolism; Embryo/metabolism*; Epithelial Cells/ultrastructure; Female; Fever*; Heat; Kinetics; Mice; Microscopy, Electron; Mitochondria/metabolism*; Research Support, U.S. Gov't, P.H.S.; Temperature; Teratogens; Time Factors

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