Study on effects of endocrine disrupter on cleft lip and/or palate.

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As an environmental factor, the inhibition of the production of urokinase-type plasminogen activator (u-PA) as a marker of vascular development was studied using bisphenol A (BPA). The u-PA production was not inhibited by BPA. On the other hand, the metabolism of folate affects the cause of cleft lip and/or palate. To clarify this point, several gene expressions related with folate metabolism were determined.It is suggested that BPA is likely to partly modulate the transcription of the genes involved in bone metabolism through retinoic acid receptor, resulting in the suppression of the development of a cleft lip and/or palate. Further, through the comprehensive screening of natural retinoic acid receptor or estrogen receptor agonists to prevent the development of a cleft lip and/or palate, we isolated a few RAR agonists from crude drugs used in Kampo medicines.