Retinoic Acid Is a Negative Regulator of sFLT1 Expression in Decidual Stromal Cells, and Its Levels Are Reduced in Preeclamptic Decidua

sFLT1 (soluble VEGF [vascular endothelial growth factor] receptor-1) levels are increased in preeclampsia—a pathological condition of pregnancy. The mechanism of sFLT1 overexpression by gestational tissues, particularly the decidua, remains unknown. Mass spectrometry measurement of the active retinoidmetabolite, all-trans retinoic acid (RA), showed significantly lower levels of RA in preeclamptic versus normotensive decidua. In this study, we investigated the involvement of RA in regulating decidualsFLT1 expression. When decidualstromal cells (DSCs) isolated from the deciduabasalis of normotensive and preeclampsiaplacentas were treated with BMS493—a pan-RAR (RA nuclear receptor) antagonist—upregulation of sFLT1 expression was observed. Conversely, treatment with RA resulted in downregulation of sFLT1 in normotensive DSCs and preeclampsiaDSCs. Unlike treatment with cAMP, which induces decidualizationwhile downregulating sFLT1, RA treatment did not alter DSC expression of prolactin—a marker of decidu...