Effect of ethanol on the development of visceral yolk sac.
BACKGROUND
Prenatal ethanol exposure can cause development retardation and malformations in human offspring. Before the formation of chorioallantoic placenta, yolk sac plays an important role in transporting nutrients from the mother to the embryo. Functional suppression of yolk sac is found to be relevant to the malformations in mammalian embryos.


METHODS
Female 8.5-day C57BL/6J mouse embryos were cultured in vitro and exposed to different doses of ethanol. The development of visceral yolk sac (VYS) was examined with light and electron microscopes. The expression profiles of some vasculogenesis-related genes were detected with reverse transcription-PCR.


RESULTS
A dose-dependent toxicity to the VYS was found, including reduced diameter, decreased protein and DNA contents, and suppressed development of vitelline vessels. The hypogenesis of VYS agreed with the retarded development and/or malformations found in the embryos. Histological and functional alterations were found in the ethanol-exposed VYS endodermal cells. The expressions of vasculogenesis-related genes, fetal liver kinase 1 (Flk1) and tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (Tie2), were repressed by ethanol.


CONCLUSIONS
Impaired structural and functional development of VYS may contribute to the teratogenic action of ethanol in mice, which may also provide a clue to the study of fetal alcohol syndrome in humans.
Xu
Yajun
Y
Department of Nutrition & Food Hygiene, Laboratory of Molecular Toxicology & Developmental Molecular Biology, School of Public Health, Peking University, Beijing, China.
Xiao
Rong
R
Li
Yong
Y
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D046149:Embryo Culture Techniques; D004622:Embryo, Mammalian / Q000187:drug effects / Q000473:pathology; D047108:Embryonic Development / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D011247:Pregnancy; D042787:Receptor, TIE-2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D015017:Yolk Sac / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure
D002492:Central Nervous System Depressants; D000431:Ethanol; D042787:Receptor, TIE-2; D040301:Vascular Endothelial Growth Factor Receptor-2