Understanding the Mechanisms of Gestational Exposure to Ultrafine Particulate Matter on Placental Development and Dysfunction in a Murine Model

Abstract

Particulate matter (PM) air pollution is of growing concern due to increasing evidence of its ability to cause adverse health effects, particularly during development. PM represents a heterogenous mixture of compounds divided into three categories based upon their size (i.e., aerodynamic diameter): coarse (2.5-10 µm), fine (<2.5 µm), and ultrafine (<0.1 µm). Currently, there is no established regulatory limit or guideline for ultrafine particulate (UFP) exposure. Recent data supports the ability of UFPs to impact the placenta directly, via particle translocation, and indirectly, through oxidative stress-related mechanisms. It is well documented that any disruption within the placenta will affect its ability to function, thus potentially negatively impacting crucial windows of fetal growth and development. Given the gap in knowledge concerning the mechanisms of action regarding UFP exposure during pregnancy on placental development, we conducted several in vivo studies in a mouse model to investigate the impact of gestational UFP exposure on signaling pathways in placental development. We sought to clarify the role of Nrf2, the master regulator of antioxidant signaling as it relates to UFP exposure. Our findings yield a greater molecular understanding of UFP-driven placental dysfunction. These outcomes confirm how UFP exposure impacts placental development and highlight the importance of the antioxidant response pathway. Ultimately, this research adds to the body of literature that can inform preventive strategies to mitigate maternal exposure and protect fetal health.