Abstract: BACKGROUND ＆ AIM: To explore the effect of alcohol on the development of mouse visceral yolk sac (VYS) during organogenesis period, and the relationship to the teratogenicity of alcohol. MATERIAL AND METHODS: 8.5 day CD-1 mouse embryos were cultured in vitro for 48 hours, with different alcohol concentrations of 0、1.0、 2.0 and 4.0 mg/ml. The developmental status of VYS and embryos were evaluated at the end of the culture. Hematoxylin and eosin (HE) staining was carried out to detect the histological alteration of VYS. Scanning and transmitting electron microscopy were performed to explore the ultrastructural alterations of endoderm cells of VYS. The expressions of a serial of vasculogenesis/angiogenesis related genes were detected with semi-quantitative RT-PCR. RESULTS: A dose-dependent toxicity to the development of VYS was abserved, including reduced yolk sac diameter, blood circulation, and protein and DNA contents. The hypogenesis of VYS agreed with the developmental retardation and malformations of the embryos. Pathological examination revealed that in the ethanol exposure groups, the endoderm layer of VYS was deranged and large intracellular vacuoles were found in the subapical area. Electron microscopy disclosed fewer microvilli and pinocytotic invaginations on the apical surface of endoderm cells. Signs of apoptosis were also found. The expressions of a series of vasculogenesis and angiogenesis related genes were detected with semi-quantitative RT-PCR. Flk1 and Tie2 gene were repressed by ethanol, which may count for the disturbance of VYS blood vessel formation. Impaired structural and functional development of VYS may contribute to the teratogenic action of ethanol. CONCLUSION: Alcohol exposure in vitro can affect the development of mouse VYS, which may contribute to the teratogenic effect of alcohol.

Key words: alcohol, visceral yolk sac, teratogenicity