Paracellular route is the major urate transport pathway across the blood-placental barrier.
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.
Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Ichiro
I
Uehara
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Toru
T
Kimura
Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Shinji
S
Tanigaki
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Toshiyuki
T
Fukutomi
Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Keiji
K
Sakai
Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Hachiouji, Tokyo, Japan.
Yoshihiko
Y
Shinohara
Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Hachiouji, Tokyo, Japan.
Kimiyoshi
K
Ichida
Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Mitsutoshi
M
Iwashita
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Hiroyuki
H
Sakurai
Paracellular; placenta; syncytiotrophoblast; urate transporter; uric acid