Cell death in rat and mouse embryos exposed to methanol in whole embryo culture

Abstract

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.

Polytopic anomalies with agenesis of the lower vertebral column

“…However, given the observation of HLXB9 (locus for dominantly inherited sacral agenesis) expression in pancreas, the well-established association between sacral agenesis and maternal insulin-dependent diabetes mellitus may be explained by a gene mutation rather than an invironmental effect [Ross et al, 1998]. Other teratogens such as alcohol and retinoic acid were reported, experimentally [Abbott et al, 1995;Padmanabhan, 1998] and clinically to cause a malformation complex similar to that seen in our cases. Thus, case 5 of Carstens and Schneider [1989] and case 3 of Hotston and Carty [1982] were sons of an alcohol-dependent mother.…”

Methanol, formaldehyde, and sodium formate exposure in rat and mouse conceptuses: A potential role of the visceral yolk sac in embryotoxicity

“…Therefore, human embryos are more likely to be directly exposed to toxicants and may be more prone to teratogenesis due to the lack of physical and metabolic protection offered by the rodent VYS. A more accurate extrapolation of rodent studies to human CH 3 OH exposure may be accomplished through the evaluation of direct exposure of the embryo proper rather than CH 3 OH exposure to the entire conceptus, as previously performed in whole embryo culture (Andrews et al, 1993, 1995, 1998; Abbott et al, 1995; Bolon et al, 1994).…”

Mutational screening of theCYP26A1gene in patients with caudal regression syndrome

“…The etiology of caudal malformation in humans remains poorly understood despite the huge amount of data available from animal models. Maternal diabetes, vascular hypoperfusion, alcohol, and RA have been suggested as causative environmental factors (Abbott et al,1995; Passarge and Lenz,1966; Padmanabhan,1998). Familial occurrence (Fullana et al,1986) suggests a genetic cause.…”