title: Expression and uptake of the thyroxine-binding protein transthyretin is regulated by oxygen in primary trophoblast placental cells.
abstract: Transplacental delivery of maternal thyroid hormones to the fetus, in particular thyroxine (T₄), is critical in ensuring normal fetal neurological development. The fetus relies on maternal T₄ till around 16 weeks gestation, but mechanisms of placental T₄ transport are not yet fully elucidated. Placenta produces, secretes and takes up the thyroid hormone-binding protein transthyretin (TTR). Many placental genes are regulated by oxygen levels, which are relatively low (1%) in the early first trimester, rising to 3% in the mid first trimester and 8% in the early second trimester and thereafter. We examined the expression and uptake of TTR in isolated primary human placental cytotrophoblast cells cultured under different oxygen concentrations (1, 3, 8, 21% O₂ and 200 μM desferrioxamine (DFO)) for 24 h. We observed sevenfold higher expression of TTR mRNA and protein levels at 1% O₂ than at 8 and 21% O₂. Significant increases were observed after culture at 3% O₂ and following DFO treatment. We observed significantly higher uptake of ¹²⁵I-TTR and Alexa-594-TTR when cells were cultured at 1 and 3% O₂ and in the presence of 200 μM DFO than at 8 and 21% O₂. When JEG-3 choriocarcinoma cells were transfected with TTR promoter reporter constructs, increased luciferase activity was measured in cells cultured at 1 and 3% O₂ in comparison to 8 and 21% O₂. We conclude that placental TTR expression and uptake is increased by the relative hypoxia observed in the first trimester of pregnancy, a time when materno-fetal T₄ transfer is the sole source of fetal T₄.
authors: School of Medicine, Royal Brisbane and Women's Hospital, The University of Queensland, Herston, Brisbane, Queensland 4029, Australia.
authors: J
authors: J
authors: Patel
authors: K A
authors: KA
authors: Landers
authors: R H
authors: RH
authors: Mortimer
authors: K
authors: K
authors: Richard
mesh_terms: D000328:Adult; D020126:Brefeldin A / Q000494:pharmacology; D015687:Cell Hypoxia; D002460:Cell Line; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D010100:Oxygen / Q000378:metabolism*; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors; D011401:Promoter Regions, Genetic / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D011228:Prealbumin; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D020126:Brefeldin A; D011393:Procollagen-Proline Dioxygenase; D003676:Deferoxamine; D010100:Oxygen