長期以來，臨床研究發現酒精會影響人類胚胎的正常發育，但是其分子機 制尚不清楚。在本研究中利用RNA 定位雜交的方式觀察酒精對於胚胎發育過程 中shh、sox9a、sox9b、col2a1、hand2 的影響，發現這些基因的表現均會受到酒 精的抑制。這項結果顯示在胚胎發育過程中，酒精透過對上述基因的影響，造成 神經脊細胞減少，細胞遷移異常，以及干擾軟骨細胞分化的現象，進而造成頭骨 發育的嚴重缺陷。此外，實驗中亦發現生長激素在腦下垂體的表現亦受到酒精抑 制。這項研究的結果成功地從基因的層次深入了解胎兒酒精中毒症候群造成頭骨 畸形及生長遲緩的病理機制。 It was known that prenatal alcohol exposure may cause serious birth defects and developmental disabilities. The molecular mechanism of this fetal alcohol syndrome still remains unclear. As revealed by whole mount RNA in situ hybridization, it was shown that expression of a number of craniofacial cartilage-related genes, including shh, sox9a, sox9b, col2a1 and hand2, were all inhibited in zebrafish embryo by alcohol exposure. It suggests that alcohol exposure may result in reducing neural crest cell production, interfering neural crest migration, preventing chondrogenesis and eventually cause craniofacial defects. In addition, the transcriptional profile of pituitary hormones were investigated by RNA in situ hybridization. It appears that only growth hormone, but not prolactin and thyroid stimulating hormone, was inhibited by alcohol exposure. The reduction of growth hormone transcription was also confirmed by real time PCR. It also appears that the expression of upstream transcription factor pit1 and downstream target gene igf1 remains unchanged. It suggests that the reduction of gh transcription is mediated by a PIT1-independent pathway. The transcriptional profile of alcohol-exposed embryo was investigated by gene microarray analysis. It appears that the expression profiles of a number of development, cellular signaling, cell growth and apoptosis related genes have be affected by 1.5% alcohol treatment. It was noted that a number of retinal-specific genes were all repressed significantly. It consists with histochemical observation that alcohol exposure results in loss lamination and disturbed differentiation. This study help us understanding the molecular mechanism of fetal alcohol syndrome.