Sexual Dimorphism of Preeclampsia-Dysregulated Transcriptomic Profiles and Endothelial Function in Fetal Endothelial Cells

Preeclampsia-offspring have increased risks of developing cardiovascular disorders in adulthood, implicating that preeclampsia programs fetal vasculature in utero. Fetal sex is associated with the risk of preeclampsia but the underlying mechanisms are unclear. We hypothesize that preeclampsia alters fetal endothelial gene expression and disturbs cytokines and growth factors-induced endothelial function in a fetal sex-specific manner. Methods: RNAseq analysis was performed with female and male unpassaged (P0) human umbilical vein endothelial cells (HUVECs) from normotensive and preeclamptic (PE) pregnancies and verified by RT-qPCR. Results: PE dysregulate 926 and 172 genes in female and male P0-HUVECs, respectively. PE differentially dysregulates cardiovascular diseases (i.e. heart failure) and endothelial function (i.e. endothelial cell migration, calcium, eNOS, and iNOS signaling)-associated genes in female and male P0-HUVECs. PE also differentially dysregulates TNF-, TGFß1-, FGF2-, and VEGFA-regulated gene networks in female and male P0-HUVECs. Conclusions: There are sexual dimorphisms of PE-dysregulated cardiovascular diseases and endothelial function-associated genes/pathways in fetal endothelial cells in association with sexual dimorphisms of PE-dysregulated fetal endothelial function. Overall design: Examination of unpassaged (P0) human umbilical vein endothelial cells (HUVECs) from normotensive and preeclamptic (PE) pregnancies with female (F) and male (M) fetuses.