School of Medicine, Royal Brisbane and Women's Hospital, The University of Queensland, Herston, Brisbane, Queensland 4029, Australia.
J Endocrinol. 2012 Feb;212(2):159-67. doi: 10.1530/JOE-11-0348. Epub 2011 Nov 1.
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.
母体甲状腺激素向胎儿的胎盘转运，特别是甲状腺素（T₄），对于确保胎儿正常的神经发育至关重要。胎儿依赖母体 T₄直到大约 16 周妊娠，但胎盘 T₄转运的机制尚未完全阐明。胎盘产生、分泌和摄取甲状腺激素结合蛋白转甲状腺素（TTR）。许多胎盘基因受氧水平调节，在妊娠早期第一阶段氧水平相对较低（1%），在妊娠中期第一阶段上升至 3%，在妊娠中期第二阶段和之后上升至 8%。我们研究了在不同氧浓度（1%、3%、8%、21%O₂和 200μM 去铁胺（DFO））下培养的分离的原代人胎盘滋养细胞中的 TTR 的表达和摄取 24 小时。我们观察到 1%O₂下 TTR mRNA 和蛋白水平的表达比 8%和 21%O₂高七倍。在 3%O₂培养和 DFO 处理后观察到显著增加。当细胞在 1%和 3%O₂培养和存在 200μM DFO 时，我们观察到 ¹²⁵I-TTR 和 Alexa-594-TTR 的摄取显著增加，而在 8%和 21%O₂时则不然。当 JEG-3 绒毛膜癌细胞用 TTR 启动子报告基因构建体转染时，与 8%和 21%O₂相比，在 1%和 3%O₂培养的细胞中测量到更高的荧光素酶活性。我们得出结论，胎盘 TTR 的表达和摄取是由妊娠早期观察到的相对缺氧增加引起的，此时母胎 T₄转移是胎儿 T₄的唯一来源。
