Open AccessParacellular route is the major urate transport pathway across the blood‐placental barrier
Author(s) -
Uehara Ichiro,
Kimura Toru,
Tanigaki Shinji,
Fukutomi Toshiyuki,
Sakai Keiji,
Shinohara Yoshihiko,
Ichida Kimiyoshi,
Iwashita Mitsutoshi,
Sakurai Hiroyuki
Publication year - 2014
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12013
Subject(s) - umbilical cord , placenta , umbilical vein , uric acid , medicine , fetus , endocrinology , syncytiotrophoblast , chemistry , andrology , pregnancy , immunology , biochemistry , biology , in vitro , genetics
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 K yorin U niversity H ospital 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 OAT 4, OAT 10, GLUT 9/ URAT v1 and ABCG 2 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.