Gestational inhalation of nanoparticles alters placental glucose transporter expression and increases glucose flux in rats

Fetal health is heavily dictated by the maternal environment. Inhaling airborne pollutants, like particulate matter, is associated with pregnancy complications and fetal developmental pathologies, including fetal growth restriction (FGR). Because fetal growth is dependent on the placental transfer of nutrients from the maternal circulation, particularly glucose, investigating glucose transport capacity is critical to understanding the development of FGR associated with gestational inhalation of particulate matter. Pregnant Sprague Dawley rats were exposed to titanium dioxide nanoparticles (9.8 ± 1.0 mg/m 3 ) to model occupational-level exposure to airborne particulates, from gestational day (GD) 5 to GD 19 via whole-body inhalation. Glucose transporters (GLUTs) 1, 3 and 4 were evaluated in term placentas on GD 20 and ex vivo placental perfusion was conducted as a functional assessment of glucose transport. Exposure resulted in a reduction in Glut3 mRNA and GLUT1 protein. However, exposed placentas exhibited a functional adaptation, characterized by increased GLUT4 expression and membrane localization of both GLUT1 and GLUT4. Placental perfusion confirmed these molecular changes, revealing increased glucose flux in exposed placentas compared to control (AUC 95% CI: 77.4 to 127.5 vs 39.1 to 73.6, respectively). Contrary to our hypothesis, exposure to these nanoparticles enhanced glucose transport across the placenta. Here we have demonstrated that inhaling airborne pollutants during pregnancy modulates placental function and nutrient transport mechanisms, which can have direct effects on fetal development. Furthermore, we provide evidence for targeted interventions, aimed at mitigating fetal developmental pathologies.