Abstract

Preeclampsia (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.