The upper lip is formed by the fusion of facial processes, a process in which many genetic and environmental factors are involved. Embryonic hypoxia is induced by uterine anemia and the administration of vasoconstrictors during pregnancy. To define the relationship between hypoxia and upper lip formation, hypoxic conditions were created in a whole embryo culture system. Hypoxic embryos showed a high frequency of impaired fusion, reflecting failure in the growth of the lateral nasal process (LNP). In hypoxic embryos, cell proliferation activity in the LNP mesenchyme was decreased following downregulation of genes that are involved in lip formation. We also observed upregulation of vascular endothelial growth factor expression along with the induction of apoptosis in the LNP. These results suggest that embryonic hypoxia during lip formation induces apoptosis in physiologically hypoxic regions, hypoxia-induced gene expression and downregulation of the genes involved in maxillofacial morphogenesis as immediate responses, followed by reduction of mesenchymal cell proliferation activity, resulting in insufficient growth of the facial processes.
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