Transcriptomic Drivers of Differentiation, Maturation, and Polyploidy in Human Extravillous Trophoblast

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.