Gestational Exposure to Air Pollutants Perturbs Metabolic and Placenta-Fetal Phenotype

Introduction: Air pollution is detrimental to a pregnancy with adverse effects in mother and child. It is also known to increase pregnancy complications including risk factors of gestational diabetes. Methods: We investigated the impact of intra-nasal instilled air pollutants upon gestational day 16-19 maternal mouse cardiovascular and metabolic status, placental nutrient transporters, and placental-fetal size and morphology. To further unravel mechanisms, we also examined placental total DNA 5’-hydroxymethylation and bulk RNA sequenced gene expression profiles. Results: Air pollution exposed pregnant mice were tachycardic, hyperglycemic, glucose intolerant and insulin resistant, with no major placental glucose and fatty acid transporter changes, except for a spatial disruption of cells expressing GLUT10 that imports L-dehydroascorbic acid in protecting against oxidative stress. Placentas revealed inflammatory cellular infiltration with associated cellular edema and necrosis, with a paucity of vascularity and hemorrhage. While individual fetal body weights increased, they suffered a reduction in brain cortical thickness. Placental total DNA 5’-hydroxymethylation was 2.5-fold higher, with perturbed gene expression profiles involving key metabolic, inflammatory, transcriptional, cellular polarizing and processing genes and pathways. Discussion: We conclude that gestational exposure to air pollutants incites a maternal inflammatory response resulting in features of maternal gestational diabetes mellitus with altered placental gene expression with associated injury to the placental-fetal unit. Thus, air pollutants adversely impact the health of mother and offspring.