Abstract
Placenta plays an essential role in pregnancy maintenance and fetal development. Therefore, it has been suggested that functional and structural abnormalities in the placenta caused by chemical substances could lead to adverse pregnancy outcomes. From this viewpoint, we have previously shown that valproic acid, which can cause congenital abnormalities and developmental toxicity, can reduce the expression level of SLC6A19 in the human choriocarcinoma cell line BeWo. However, the induction mechanism is not clear. Here, we focused on the HDAC inhibitory effect of valproic acid and attempted to elucidate the mechanism by which valproic acid decrease SLC6A19 expression. First, we evaluated the HDAC2 inhibitory effect of three chemicals; valpromide, an amide derivative of valproic acid that does not have an HDAC inhibitory effect, valnoctamide, a structural isomer of valpromid, and valproic acid. Only valproic acid inhibited HDAC2 activity in a concentration-dependent manner. Then, BeWo cells were treated with each chemical for 72 h, and the expression level of SLC6A19 was assessed by real-time RT-PCR. In valproic acid-treated group, the expression of SLC6A19 was decreased, however, there was no significant change in that of the valpromide- and valnoctamide-treated groups. These results suggest that the HDAC2 inhibitory effect of valproic acid might be involved in the decrease in SLC6A19 expression caused by valproic acid. In the future, we attempt to identify the transcription factors involved in regulating SLC6A19 expression.
