title: Effect of oxygen concentrations on sodium iodide symporter expression and iodide uptake and hCG expression in human choriocarcinoma BeWo cells.
abstract: Normal human fetal development requires an adequate supply of thyroid hormone from conception. Until about 16 wk gestation this is supplied entirely by placental transfer of maternal hormone. Subsequently, the fetal thyroid synthesizes thyroid hormones, requiring a supply of maternal iodide. Trophoblast iodide transfer is mediated by the apical sodium iodide symporter (NIS). Placental oxygen levels are low in early pregnancy (~1%), rising with placental vascularisation to a plateau of ~8% at about 16 wk. Although the impact of these changing oxygen levels on placental implantation is well recognized, effects on trophoblast materno-fetal exchange are less understood. We investigated expression of the NIS regulator hCG, NIS mRNA expression, and I(125) uptake in choriocarcinoma BeWo cells (a model of the trophoblast) cultured in 1 and 8% oxygen and in room air (21% oxygen). Expression of NIS and hCG mRNA and protein was low at 1% oxygen but rose significantly at 8 and at 21%. This was reflected in significant increases in I(125) uptake. Desferrioxamine, an iron chelator and hypoxia mimic, decreased NIS and hCG expression and I(125) uptake in BeWo cells. NIS expression and I(125) uptake in cells grown at 1% oxygen were not increased by addition of hCG (2,500 IU/l). We infer that placental NIS mRNA and protein expression are regulated by oxygen, rising with vascularization of the placenta in the late first trimester, a time when fetal iodide requirements are increasing.
authors.affiliation: Conjoint Endocrine Laboratory, Royal Brisbane and Women’s Hospital, Herston, Australia.
authors.forename: Huika
authors.initials: H
authors.lastname: Li
authors.forename: Kelly
authors.initials: K
authors.lastname: Landers
authors.forename: Jatin
authors.initials: J
authors.lastname: Patel
authors.forename: Kerry
authors.initials: K
authors.lastname: Richard
authors.forename: Robin H
authors.initials: RH
authors.lastname: Mortimer
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D006063:Chorionic Gonadotropin / Q000096:biosynthesis*; D003676:Deferoxamine / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007118:Immunoassay; D007454:Iodides / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007502:Iron Chelating Agents / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D010100:Oxygen / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000096:biosynthesis* / Q000235:genetics; D013963:Thyroid Hormones / Q000096:biosynthesis; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000235:genetics; D000099209:Sodium-Iodide Symporters
chemical_list: D006063:Chorionic Gonadotropin; D003676:Deferoxamine; D007454:Iodides; D007457:Iodine Radioisotopes; D007502:Iron Chelating Agents; D008565:Membrane Proteins; D010100:Oxygen; D027981:Symporters; D013963:Thyroid Hormones; D001613:beta 2-Microglobulin; D000099209:Sodium-Iodide Symporters