Biology subjects

Mohammadkhani, S.

Publications and source records attributed to Mohammadkhani, S..

2 recordsLinked to original sources

bioRxiv2025

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.

developmental biology↗

bioRxiv2025

Maternal High Fat Diet and Acute Viral Mimic Exposure Impact Placental Inflammation, Lipid Peroxidation, and Cellular Dynamics Across Mouse Pregnancy

Maternal obesity and viral infection induce placental inflammation, but how their co-exposure influence fetoplacental development remains unclear. We hypothesized 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. 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) 24h 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-1{beta} were measured by qPCR. Data were analysed by linear mixed models (p[≤]0.05). At 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-1{beta} mRNA expression, ir-4-HNE in the JZ and ir-Caspase-3 in the LZ. Maternal HF diet and infection exert distinct effects on the placenta across gestation, suggesting that maternal overnutrition might reduce the placentas capacity to handle adverse exposures, which may increase susceptibility to poor fetal outcomes.

developmental biology↗