Combined Metabolic and Viral Insults in Pregnancy Disrupt Specific Placental Nutrient Transporter Systems in Mice

The placenta adapts to support nutrient transport to meet the demands of the growing fetus. Maternal obesity and viral infection are associated with adverse fetoplacental development. How co-exposure affects placental morphology and nutrient transport across gestation remains unclear. We hypothesise that co-exposure would have a greater impact on placental morphology and nutrient transporter expression than either of the exposures alone. C57BL/6J mice were fed a control (CON) or high-fat (HF) diet before and throughout pregnancy and exposed to poly(I:C) or vehicle at gestational days (GD) 12.5, 15.5, or 18.5. Placental morphology, folate and fatty acid transporter mRNA expression and localisation were evaluated by haematoxylin and eosin staining, immunohistochemistry (reported as % immunoreactivity (ir)-area stained), and qPCR, respectively. At GD12.5, HF diet associated with reduced junctional zone (JZ) and labyrinth zone (LZ) area and increased maternal blood space, followed by reduced fetal blood space at GD15.5 and increased JZ and LZ area size by GD18.5. HF diet and viral infection independently associated with increased placental Fat/Cd36 mRNA expression at GD12.5. However, HF diet and infection associated with increased ir-FR- while HF diet alone decreased ir-PCFT at GD12.5. By GD15.5, HF diet associated with reduced placental ir-FR- but increased ir-PCFT. At GD18.5, infection associated with reduced Rfc1 mRNA expression. HF diet and infection associated with greater prevalence of SGA and LGA fetuses, particularly at GD18.5. Obesity and infection independently and synergistically disrupted placental morphology and nutrient transporter expression in a zone- and gestational age-specific manner, with consequences for fetal growth across gestation.