Maternal High Fat Diet and Acute Viral Mimic Exposure Impact Placental Inflammation, Lipid Peroxidation and Cellular Proliferation-to-Death Ratio Across Mouse Pregnancy.

problemMaternal obesity and viral infection induce placental inflammation, but how their co-exposure influence fetoplacental development remains unclear. We hypothesised that maternal high fat (HF) diet and viral infection would independently induce placental inflammation and lipid peroxidation, reduce antioxidant defence, and cellular turnover. Further, HF diet would compromise placental capacity to adapt to infection. METHOD OF STUDY: Female C57BL/6J mice were fed a control (CON) or 62% HF diet six weeks before and throughout pregnancy and injected with poly(I:C) (viral mimic) or vehicle (VEH) 24 h before sacrifice at gestational days (GD) 12.5, 15.5, and 18.5 (n = 5-8/group/GD). Placental inflammasome (NLRP3), oxidative stress (4-HNE), antioxidant defence (GPx-4), and cellular proliferation-to-death ratio (Ki-67, Caspase-3) were assessed by immunohistochemistry, and mRNA expression of Tlr3, Irf3, Tlr4, Tirap, and Il-1β were measured by qPCR. Data were analysed by linear mixed models (p ≤ 0.05).

resultsAt GD12.5, infection was associated with increased Tlr3 mRNA and immunoreactive (ir)-4-HNE, and reduced ir-GPx-4 expression in the placental labyrinth zone (LZ). By GD15.5, HF diet was associated with increased ir-NLRP3 in both LZ and junctional zones (JZ). Exposure to infection alone and co-exposure to HF diet and infection further increased LZ ir-NLRP3. At GD18.5, HF diet was associated with increased Tirap and Il-1β mRNA expression, ir-4-HNE in the JZ and ir-Caspase-3 in the LZ.

conclusionsMaternal HF diet and infection exert distinct effects on the placenta across gestation, suggesting that maternal overnutrition might reduce the placenta's capacity to handle adverse exposures, which may increase susceptibility to poor fetal outcomes.