Decidual cells from women with preeclampsia exhibit inadequate decidualization and reduced sFlt1 suppression

Abstract Uterine stromal cell decidualization of maternal tissue is essential for implantation of and local adaptation to the fetal allograft, as well as growth and maintenance of the placenta in healthy pregnancies. Maternal defects in decidualization have been suggested as a possible driver of preeclampsia. Preeclampsia (PE) pregnancies demonstrate shallow implantation, inadequate spiral artery remodeling, and elevated levels of the anti-angiogenic protein, sFlt1. To test whether stromal cells (DSCs) isolated from PE placentas exhibit inadequate re-decidualization and increased expression of sFlt1, DSCs from normotensive (NT-DSCs) and PE (PE-DSCs) placentas were treated for 8 days (D8) with cAMP to induce decidualization and levels of decidualization markers (PRL, IGFBP1, VEGF) and sFlt1 were measured at day 0 (D0), D8, and after reversal of treatment. NT-DSCs achieved statistically significant elevations in PRL and IFGBP1 expression (25.72 [5.78–50.04], p  = 0.0008 and 92.09 [1.79–543.10], p  = 0.005). PE-DSCs increased PRL and IFGBP1 expression to 6.15 [2.30–10.73] ( p  = 0.18) and 8.67 [1.64–376.10] ( p  = 0.04). NT-DSCs reduced sFlt1 expression at D8 to 0.25 [0.17–0.49] ( p  = 0.0021) compared to 0.31 [0.25–0.82] ( p  = 0.087) in PE-DSCs. These results show that, when induced to decidualize, PE-DSCs fail to increase expression of decidualization markers to levels achieved by NT-DSCs. sFlt1 expression is higher in PE-DSCs during decidualization, suggesting inadequate suppression during the crucial implantation period. These defects at the maternal fetal interface may lead to the failed spiral artery modification, decreased placental invasion of the uterus, and elevated circulating sFlt1 levels seen in PE pathology.