Transcriptomic Drivers of Differentiation, Maturation, and Polyploidy in Human Extravillous Trophoblast [SNP array]

During pregnancy, normal extravillous trophoblast (EVT) invade the endomyometrium of the maternal uterus and remodel the spiral arteries to control blood supply and nutrient transfer. Recent reports have described first trimester EVT as polyploid and senescent. Here we extend these earlier reports by performing comprehensive profiling of the genomic organization and transcriptome of first trimester EVT and term EVT. We define pathways and gene regulatory networks involved in both initial differentiation and maturation of this important trophoblast lineage at the maternal-fetal interface. Our results suggest that like first trimester EVT, term EVT undergo senescence and endoreduplication, are primarily tetraploid, and lack high rates of copy number variations. Additionally, we have highlighted senescence and polyploidy-related genes, pathways, networks, and transcription factors that appeared to be important in normal EVT differentiation and maturation and have validated a critical role for the unfolded protein response in EVT differentiation. A total of 13 samples were analyzed (two first trimester EVT, two first trimester CTB, three term EVT, three term CTB, and three umbilical cord MSC). The samples were isolated from a total of five placentas (two first trimester placentas and three term placentas). Matched EVT and CTB were isolated from all five placentas and MSCs were isolated from the three term placentas as controls. One of the CTB samples (1391) was removed from analysis due to poor call rates.