Urate, the final oxidation product of
purine metabolism, is excreted into urine in humans. Clinically, increased serum
urate levels are indicative of
pregnancy-induced hypertension (PIH). However, how
urate is handled in the placenta is still largely unknown. In this study, we compared maternal serum
urate levels with those of umbilical cord blood and investigated
urate transport mechanisms in BeWo cells, a trophoblast-derived cell line. The maternal and umbilical cord blood samples and placentas were collected from patients undergoing
cesarean section at
Kyorin University Hospital after obtaining informed consents. There were no significant differences in serum
urate levels between maternal blood and umbilical cord blood, and between umbilical cord vein and arterial blood, suggesting that
urate is freely movable at the placenta and that fetus is not a major source of
urate production. RT-PCR and immunohistochemistry showed that
urate transporters including OAT4, OAT10, GLUT9/URATv1 and ABCG2 were expressed in the syncytiotrophoblast cells in the placenta as well as BeWo cells. Despite expressing aforementioned
urate transporters BeWo cells did not take up
urate. After confirming the formation of tight junctions of these cells cultured on the transwell,
urate transport between upper and lower chambers was measured.
Urate moved through BeWo cell monolayers with nonsaturation kinetics and this movement was observed even when the cells were incubated at 4°C, suggesting that
urate moves through the paracellular route by simple diffusion.