Early-life Exposure to Arsenic Primes the Offspring to Increased Asthma Risk: Transcriptome and Epigenome Analysis

Inorganic arsenic (iAs) in drinking water is a global health concern. This study tests whether maternal exposure to iAs in drinking water at the WHO provisional level (10 microgram/L) increases offspring asthma risk via epigenetic reprogramming. F1 mice prenatally exposed to iAs were analyzed at 5 months for blood transcriptome and methylome changes and challenged with house allergens before lung function testing. Prenatal iAs exposure led to increased airway hyperresponsiveness (AHR) and altered inflammation gene expression and DNA methylation changes. Notably, miR-101c was epigenetically reprogrammed early in development, with persistent downregulation in both target (fetal and adult lungs) and surrogate (amniotic fluid and blood) tissues. These changes correlated with increased allergic AHR and TGFβ pathway dysregulation. Findings suggest that maternal iAs exposure primes offspring for asthma risk through epigenetic alterations and may inform risk assessment and biomarker development in affected communities.