Bidart J M, Lacroix L, Evain-Brion D, Caillou B, Lazar V, Frydman R, Bellet D, Filetti S, Schlumberger M
Department of Clinical Biology, Institut Gustave-Roussy, Villejuif, France.
J Clin Endocrinol Metab. 2000 Nov;85(11):4367-72. doi: 10.1210/jcem.85.11.6969.
Placental iodide transport is critical for the fetal thyroid function, but the molecular mechanisms of this transport are not understood. The expression of two recently identified iodide transporters, namely the sodium/iodide symporter (NIS) and pendrin, the product of the gene responsible for the Pendred syndrome (PDS), was studied using real-time kinetic quantitative PCR and immunohistochemistry 1) in placental tissues collected at different gestational ages and 2) in primary cultures of villous cytotrophoblast cells (VCT) that differentiate and fuse over 2-3 days in vitro to form villous syncytiotrophoblast (VSCT) cells. Both NIS and PDS genes are expressed in placenta, albeit at low levels compared with those in thyroid tissue. NIS gene expression in placental samples from first trimester and term pregnancies was similar. In contrast, the expression of PDS gene was higher in term than in first trimester pregnancy samples. In vitro, NIS gene was expressed at a high level in VCT obtained from first trimester pregnancy, and its expression decreased by 3- to 4-fold during the differentiation of VCT in VSCT. Expression of NIS was lower (up to 30-fold) in VCT obtained in placental samples from third trimester than from first trimester pregnancy. In contrast, the expression of PDS gene was low in VCT and increased by 5- to 10-fold during VSCT formation; this was observed in cells isolated from placental samples of both first trimester and term pregnancies. Immunohistochemical analysis showed that NIS protein was present on the entire membrane of VCT, whereas pendrin was mainly located at the brush border membrane of VSCT, facing the mother. In conclusion, 1) NIS and PDS genes are differently expressed in the placenta during gestation; and 2) whereas pendrin is expressed at the brush border membrane of syncytiotrophoblast cells, NIS protein is mainly located in the cytotrophoblast layer.
胎盘碘转运对胎儿甲状腺功能至关重要，但其转运的分子机制尚不清楚。利用实时动力学定量PCR和免疫组织化学方法，研究了最近发现的两种碘转运体的表达情况，这两种转运体分别是钠/碘同向转运体（NIS）和与 Pendred 综合征（PDS）相关基因的产物pendrin：1）在不同孕周采集的胎盘组织中；2）在绒毛细胞滋养层细胞（VCT）的原代培养物中，VCT 在体外 2 - 3 天内分化并融合形成绒毛合体滋养层（VSCT）细胞。NIS 和 PDS 基因在胎盘中均有表达，尽管与甲状腺组织相比表达水平较低。孕早期和足月妊娠胎盘样本中 NIS 基因表达相似。相比之下，足月妊娠样本中 PDS 基因的表达高于孕早期。在体外，孕早期妊娠获得的 VCT 中 NIS 基因高水平表达，在 VCT 分化为 VSCT 过程中其表达下降 3 至 4 倍。孕晚期胎盘样本获得的 VCT 中 NIS 表达低于孕早期（高达 30 倍）。相反，PDS 基因在 VCT 中表达较低，在 VSCT 形成过程中增加 5 至 10 倍；在孕早期和足月妊娠胎盘样本分离的细胞中均观察到这种情况。免疫组织化学分析表明，NIS 蛋白存在于 VCT 的整个细胞膜上，而 pendrin 主要位于 VSCT 面向母体的刷状缘膜上。总之，1）妊娠期间 NIS 和 PDS 基因在胎盘中表达不同；2）pendrin 在合体滋养层细胞的刷状缘膜表达，而 NIS 蛋白主要位于细胞滋养层。
