PM_2.5 exposure induces functional alterations in pregnant rats heart and in human stem cell derived cardiac spheroids

Air pollution is a major cardiovascular risk factor, with particulate matter (PM) posing significant threats. The Po Valley remains among Europe's most polluted areas. While PM₂.₅ is linked to cardiac dysfunction, its effects during pregnancy-especially under hypertensive conditions-are poorly defined. We investigated how prolonged PM exposure from Milan's urban area affects cardiac electromechanical function in pregnant normotensive and hypertensive rats, and in a human embryonic stem cell-derived 3D cardiac spheroid. Pregnant normotensive and hypertensive (SHR) rats were exposed to saline solutions w/wo PM (2 mg/kg) three times weekly for 19 days. Cardiac spheroids were cultured in DMEM w/wo PM (10-50 µg/mL) for 8 days. We assessed cardiac function via in-vivo epicardial mapping and in-vitro optokinematic analysis. Inflammatory, toxicological, and molecular profiles were evaluated. Machine learning classified electrogram profiles in PM-exposed versus unexposed rats. In SHR rats, PM exposure increased rheobase (+ 39%), current threshold (+ 32%), and chronaxie (+ 71%), with a 21% rise in effective refractory period. Conduction velocity and anisotropy were also altered. Machine learning achieved > 86% and > 77% classification accuracy in normotensive and SHR, respectively. In human cardiac spheroids derived from embryonic stem cells, short-term PM exposure impaired relaxation (- 36% at 10 µg/mL; - 21.5% at 20 µg/mL) and contraction amplitude (- 42% and - 62%, respectively). Long-term evaluation disrupted calcium transients (- 20% and - 15%) and altered IL-6. Gene expression revealed dysregulation of calcium-handling genes. These findings emphasize the heightened risks of PM exposure during gestation, particularly in preeclampsia, and support the need for public health strategies to protect maternal and fetal cardiovascular health.