Abstract
Tryptophan maintains placental function through its antioxidant properties, and its metabolites such as serotonin and kynurenine are essential for the development of fetal central nervous system. Thus, the supply of tryptophan through its transporter from mother to fetal is important for fetal growth and maintenance of pregnancy. From this viewpoint, abnormal expression or malfunction of placental tryptophan transporter could lead to fetal growth restriction or abortion. However, there is little information about the effects of chemicals having reproductive toxicity on placental tryptophan transporter. Here, we evaluated the effects of valproic acid on placental tryptophan transporter.
First, BeWo cell was treated with valproic acid for 24 hours, and the expression level of the major placental tryptophan transporters was analyzed. Real time RT-PCR analysis found that valproic acid significantly decreased only the expression level of SLC6A19. Then, tryptophan uptake into cells was assessed by LC-MS/MS, and the results showed that valproic acid decreased the amount of intracellular tryptophan in a time-dependent manner. Moreover, the amounts of serotonin and kynurenine was also decreased in valproic acid-treated group. These results suggest that valproic acid reduced SLC6A19 mRNA expression and decreased intracellular tryptophan and its metabolite levels. Now, we try to reveal the relationship between downregulation of placental SLC6A19 expression and valproic acid-induced reproductive toxicity in vivo.
