Maternal PM2.5 Exposure and Cardiac Developmental Abnormalities in Fetuses and Neonates: Progressive Activation of the Complement and Coagulation Cascade

Emerging studies indicate a positive correlation between maternal PM_2.5 exposure and an increased risk of congenital heart diseases (CHDs). However, the developmental origins in fetal and neonatal offspring, as well as the underlying mechanisms, remain elusive. To bridge this gap, we established an animal model of maternal PM_2.5 exposure and confirmed its adverse effects on cardiac function and structure in neonates, primarily left ventricular systolic and diastolic dysfunction and myocardial hypertrophy in both male and female offspring, characterized by thick ventricular walls and narrowed ventricular chambers at embryonic (E) day 18.5. Then, combining transcriptional profiling and immunohistochemical analyses, we found that the upregulation of myosin-related genes was a key mediator in these myocardial contraction abnormalities. Importantly, using time-series transcriptome analysis across critical windows of cardiac development (E10.5, E14.5, and E18.5), we uncovered that the complement and coagulation cascade signaling pathways were progressively activated, triggering cellular inflammation and lysis and upregulating myosin genes, which ultimately contributed to compensatory cardiac hypertrophy and cardiac dysfunction. This work provides a comprehensive perspective for local governments and clinicians to control and prevent CHD burden in polluted areas.