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

Area of Science:

• Environmental Health
• Toxicology
• Epigenetics

Background:

• Inorganic arsenic (iAs) in drinking water poses a global health risk.
• Epigenetic mechanisms are crucial in mediating environmental exposures and disease development.

Purpose of the Study:

• To investigate if maternal exposure to inorganic arsenic (iAs) at the WHO provisional level (10 µg/L) increases offspring asthma risk.
• To explore the role of epigenetic reprogramming, specifically DNA methylation and microRNA changes, in mediating this risk.

Main Methods:

• F1 mice underwent prenatal exposure to iAs in drinking water.
• Transcriptome and methylome analyses were performed on blood samples at 5 months.
• Mice were challenged with house allergens, followed by lung function testing.

Main Results:

• Prenatal iAs exposure resulted in increased airway hyperresponsiveness (AHR) and altered inflammation gene expression.
• Significant DNA methylation changes were observed, including the downregulation of miR-101c.
• miR-101c downregulation persisted in fetal and adult lung tissues, amniotic fluid, and blood, correlating with allergic AHR and TGFβ pathway dysregulation.

Conclusions:

• Maternal iAs exposure can prime offspring for asthma development through epigenetic alterations.
• These findings highlight the potential for iAs to disrupt normal development and increase susceptibility to allergic diseases.
• The study suggests miR-101c and TGFβ pathway as potential biomarkers for iAs-induced asthma risk assessment.