# Impact of Maternal Arsenic Exposure on Offspring's Epigenetic Reprogramming of Allergic Airway Disease

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $459,440

## Abstract

PROJECT SUMMARY
Arsenic in food and drinking water is a major global health concern. It is estimated that over 200 million
individuals are exposed to inorganic arsenic (iAs) at levels above the WHO provisional guideline value of 10µg/L
(ppb). Epidemiological and laboratory studies have suggested that prenatal exposure to low-to-moderate levels
of inorganic arsenic (iAs) may increase the risk of adverse health effects during early childhood as well as later
in life. However, there are limited research examining how arsenic exposure promotes allergic airway diseases
such as asthma, although there is growing documentation that arsenic exposure is associated with respiratory
symptoms. Our previous work, demonstrated in animal model, suggests that maternal exposures to house
allergens affect the immunological sensitization and lung growth of the neonate through epigenetic modifications
of the fetal gene transcription; which determines the offspring susceptibility to allergic airway
hyperresponsiveness (AHR). Certainly, these findings point to the epigenetic mechanism a possible mediator of
the multigenerational effect of environmental stressors on offspring’s asthma disease susceptibility. It has been
demonstrated that in utero exposure to iAs modified the structure and function of the postnatal lungs, which may
predispose the offspring to pulmonary dysfunction in adulthood. Nevertheless, less is known about how early-
life exposure to iAs promotes epigenetic regulation of allergic airway disease. We hypothesize that maternal iAs
exposure increases offspring asthma risk, in part through placental stress, which modulates epigenetic
reprograming of fetal lung development and later-life AHR phenotypes. This novel hypothesis will be tested via
two specific aims.
Specific Aim 1 is: To examine the epigenetic effect of iAs exposure on offspring lung function across the life
course and subsequent generations. We will define the critical window(s) of iAs exposure that results in later
sensitivity in asthma via epigenetic modification at lung genome. Additionally, we propose Specific Aim 2: To
investigate the influence of placental oxidative stress on epigenetic regulation of fetal lung development. In this
proposal, we will assess maternal placental function throughout the gestation and offspring’s lung function across
the adult life, using state-of-the-art physiological, molecular and epigenomic approaches. We will also determine
if the inheritance of epigenetic changes and sensitivity in the AHR of their offspring could be attenuated by
reducing placental reactive oxygen species. Taken together, our findings will allow us to not only understand the
epigenetic mechanisms by which maternal exposure to iAs reprograms the lung genome, but also how these
epigenetic changes are inherited by subsequent generations. We will provide a unique set of lung epigenetic
signatures and placental signatures for asthma risk and iAs exposure assessment, as well as considerable...

## Key facts

- **NIH application ID:** 10897078
- **Project number:** 5R01ES034760-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Wan-yee Tang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $459,440
- **Award type:** 5
- **Project period:** 2023-08-02 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10897078

## Citation

> US National Institutes of Health, RePORTER application 10897078, Impact of Maternal Arsenic Exposure on Offspring's Epigenetic Reprogramming of Allergic Airway Disease (5R01ES034760-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10897078. Licensed CC0.

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