Severe Preeclampsia is Associated with Alterations in Cytotrophoblasts of the Smooth Chorion

Preeclampsia (PE), which affects ~8% of first pregnancies, is associated with faulty placentation. Extravillous cytotrophoblasts (CTBs) fail to differentiate properly, contributing to shallow uterine invasion and deficient spiral artery remodeling. We studied the effects of severe PE (sPE) on the smooth chorion portion of the fetal membranes. The results showed a significant expansion of the CTB layer. The cells displayed enhanced expression of stage-specific antigens that extravillous CTBs normally up regulate as they exit the placenta. Transcriptomics revealed the dysregulated expression of many genes (e.g., placental proteins, markers of oxidative stress). We confirmed a sPE-related increase in production of PAPPA1, which releases IGF-1 from its binding protein. IGF1 enhanced proliferation of smooth chorion CTBs (schCTB), a possible explanation for expansion of this layer, which may partially compensate for the placental deficits. To gain a better understanding of the molecular mechanisms behind the observed schCTB alterations in sPE, we used a laser capture microdissection approach to isolate this population of cells from the fetal membranes of sPE, nPTB, and second trimester (STM) pregnancies (n=4/group) and performed whole-transcipt genome-wide profiling of total RNA using the Affymetrix GeneChip Human Gene ST 2.0