High-fat diet induces pre-eclampsia like phenotypes associated with impaired decidualization and NF-κB activation

Pre-eclampsia (PE), a life-threatening hypertensive disorder of pregnancy, remains a leading cause of maternal-fetal morbidity with unclear pathogenesis. While traditional studies focus on placental dysfunction, the critical role of decidualization-a prerequisite for placental implantation-has been underemphasized. Here, we demonstrate that a high-fat diet (HFD) predisposes mice to PE-like phenotypes, including hypertension, proteinuria, glomerular injury, and placental-fetal growth restriction, which are accompanied by impaired decidualization. HFD triggers robust inflammatory responses in decidual tissue, evidenced by upregulated IL-1β/IL-6/TNF-α and hyperactivated NF-κB signaling, which correlate with reduced expression of decidualization regulators (Bmp2, Wnt4) and marker genes (Dtprp, Prl8a2). These changes lead to compromised decidual vascularization, reduced polyploid cell differentiation, and impaired placental morphogenesis. Our findings reveal a novel association whereby HFD-induced inflammation is linked to disrupted decidual-placental crosstalk via NF-κB activation, providing mechanistic insights into PE pathogenesis and highlighting decidualization as a potential therapeutic target.