IGFBP3 repression driven by inflammation links air pollution to placental and developmental defects

Air particulate matter (PM2.5 and PM10), can cross the placental barrier, triggering oxidative stress and inflammation that compromise fetal development. These insults lead to placental dysfunction and complications including preterm birth, low birth weight, and preeclampsia. In cell line and placental explant models, urban particulate matter (UPM) increased pro-inflammatory cytokines and oxidative stress pathways, impairing trophoblast invasion, angiogenesis, and nutrient transport, while also altering epigenetic modifications and endoplasmic reticulum function. Rodent studies revealed reduced litter size, placental abnormalities, and fetal growth arrest along with postnatal neurodevelopmental alterations. Human cohorts from high-exposure regions showed elevated low birth weight rates. Proteomic and transcriptomic analyses of rat placenta revealed an inflammatory signature and altered metabolic networks, while gut microbiome dysbiosis suggested links to metabolic disturbances. Importantly, transcriptomic analysis identified IGFBP3 as a major downregulated gene following UPM exposure. IGFBP3, a key regulator of IGF bioavailability, was suppressed by IL1β, establishing inflammation-driven repression as the mechanism. These findings underscore UPM's multidimensional impact on maternal-fetal health and highlight preventive strategies as urgent priorities.