Alterations in mitochondrial morphology are associated with hyperthermia-induced apoptosis in early postimplantation mouse embryos.
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.
Kim
Won-Kyu
WK
Birth Defects Research Laboratory, Division of Genetics and Development, Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA.
Mirkes
Philip E
PE
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D045304:Cytochromes c / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism*; D004847:Epithelial Cells / Q000648:ultrastructure; D005260:Female; D005334:Fever; D006358:Hot Temperature; D007700:Kinetics; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism*; D013696:Temperature; D013723:Teratogens; D013997:Time Factors
D013723:Teratogens; D045304:Cytochromes c