Department of Obstetrics and Gynecology, Hackensack University Medical Center, Hackensack, New Jersey, USA.
Department of Pathology, Hackensack University Medical Center, Hackensack, New Jersey, USA.
Biol Reprod. 2018 Aug 1;99(2):409-421. doi: 10.1093/biolre/ioy042.
Differentiation of first trimester human placental cytotrophoblast (CTB) from an anchorage-dependent epithelial phenotype into the mesenchymal-like invasive extravillous trophoblast (EVT) is crucial in the development of the maternal-fetal interface. We showed previously that differentiation of first trimester CTB to EVT involves an epithelial-mesenchymal transition (EMT). Here we compare the epithelial-mesenchymal characteristics of CTB and EVT derived from normal third trimester placenta or placenta previa versus abnormally invasive placenta (AIP). CTB and EVT were isolated from normal term placenta or placenta previa following Caesarean section and EVT from AIP following Caesarean hysterectomy. Cell identity was validated by measurement of cytokeratin-7 and HLA-G. Comparing normal term CTB with EVT from normal term placenta or placenta previa for differential expression analysis of genes associated with the EMT showed changes in >70% of the genes probed. While demonstrating a mesenchymal phenotype relative to CTB, many of the gene expression changes in third trimester EVT were reduced relative to the first trimester EVT. We suggest that third trimester EVT are in a more constrained, metastable state compared to first trimester equivalents. By contrast, EVT from AIP demonstrate characteristics that are more mesenchymal than normal third trimester EVT, placing them closer to first trimester EVT on the EMT spectrum, consistent with a more invasive phenotype.
人类胎盘细胞滋养层（CTB）从锚定依赖性上皮表型分化为间质样侵袭性绒毛外滋养层（EVT），这对于母体-胎儿界面的发育至关重要。我们之前已经表明，CTB 向 EVT 的分化涉及上皮-间充质转化（EMT）。在这里，我们比较了来自正常足月胎盘或前置胎盘与异常侵袭性胎盘（AIP）的 CTB 和 EVT 的上皮-间充质特征。CTB 和 EVT 是从正常足月剖宫产胎盘或前置胎盘中分离出来的，而 EVT 是从 AIP 剖宫产子宫切除术获得的。通过测量细胞角蛋白-7 和 HLA-G 来验证细胞的身份。比较正常足月 CTB 与正常足月胎盘或前置胎盘来源的 EVT，对 EMT 相关基因的差异表达分析显示，超过 70%的探针基因发生了变化。虽然与 CTB 相比，第三 trimester EVT 表现出间充质表型，但与第一 trimester EVT 相比，许多基因表达变化减少。我们认为，与第一 trimester EVT 相比，第三 trimester EVT 处于更受限、更稳定的状态。相比之下，AIP 的 EVT 表现出比正常第三 trimester EVT 更具间充质特征，使它们在 EMT 谱上更接近第一 trimester EVT，与更具侵袭性的表型一致。
