Cell death in rat and mouse embryos exposed to methanol in whole embryo culture.
Methanol induces developmental toxicity in rats and mice producing exencephaly, cleft palate, cervical skeletal defects, reduced body weight, and increased embryo/fetal death. Exposure to methanol in whole embryo culture also induces developmental retardation, dysmorphogenesis, and embryo lethality. In the present study, cultured rat and mouse embryos were exposed to methanol and subsequently observed for morphological effects and increased cell death using modified Feulgen staining which allowed nuclei throughout the embryo to be examined in situ. Growth and developmental scores were reduced by methanol in both rat and mouse embryos and the mouse embryos were affected at lower concentrations when compared to the rat. Methanol increased cell death in specific regions of both rat and mouse embryos, including the forebrain, the visceral arches, otic and optic placodes. These regions form derivatives which manifest morphological abnormalities following exposure in vivo. Methanol did not increase cell death in the neuroepithelium or neural folds and neural tube defects cannot be explained by excess cell death. The results of this study suggest that increased cell death in specific regions of the exposed embryos has a role in producing cranial malformations, abnormalities of the eye and ear, and cleft palate.
Abbott
B D
BD
Developmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Ebron-McCoy
M
M
Andrews
J E
JE
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000473:pathology; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D008297:Male; D000432:Methanol / Q000633:toxicity*; D051379:Mice; D009924:Organ Culture Techniques; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000432:Methanol