# Examining tissue-specific DNA methylation after prenatal exposure to arsenic among infants with spina bifida

> **NIH NIH R21** · BOSTON CHILDREN'S HOSPITAL · 2021 · $216,875

## Abstract

PROJECT SUMMARY/ABSTRACT
Arsenic contamination in drinking water continues to be a major health threat worldwide. An emerging
hypothesis is that arsenic acts via the epigenome, the multitude of compounds that affect DNA transcription of
specific genes but do not alter DNA sequence. Better understanding of this important potential mechanism of
arsenic toxicity is essential to design strategies to prevent and treat arsenic-related diseases.
Neural tube defects, including spina bifida and anencephaly, are common and severe birth defects that occur
when the embryonic precursors to the brain and spinal cord do not properly develop. Neural tube defects are
increasingly considered to be among the sequelae of arsenic exposure. In this R21 application, we test the
hypothesis that arsenic's effects on the developing nervous system are mediated through the epigenome. We
propose to use readily accessible nervous system tissue that is exposed as a result of the birth defect to test
our hypotheses.
In this application, we establish a new basic science-clinical science collaboration to determine DNA
methylation patterns from various tissues from a human population of infants with myelomeningocele, a
common and severe form of neural tube defect. Our clinical group is currently conducting an epidemiological
study in Bangladesh to determine whether maternal arsenic exposure through contaminated drinking water
increases the risk of myelomeningocele. We have recently started collecting discarded tissue from surgical
closure of the myelomeningocele, and these samples provide a unique opportunity to investigate tissue-
specific epigenetic patterns. We propose a series of pilot studies that will whole genome bisulfite sequencing
(WGBS), a new and innovative method that enables investigation of DNA methylation at a single-nucleotide
resolution, to examine DNA methylation in candidate genes known to be important in neural tube defects in the
blood and nervous system tissue of affected infants.
These high risk, high reward studies will identify genes that are differentially methylated in relation to arsenic
exposure and phenotype, as well as test the hypothesis that neuroepithelial tissue provides a unique window
into the study of human neural tube defects. These studies will also provide important preliminary data for
future collaborative projects such as epigenome-wide association studies (EWAS). Such studies are highly
likely to provide new targets for preventive interventions.

## Key facts

- **NIH application ID:** 10217141
- **Project number:** 5R21ES030784-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Maitreyi Mazumdar
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $216,875
- **Award type:** 5
- **Project period:** 2020-07-16 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217141

## Citation

> US National Institutes of Health, RePORTER application 10217141, Examining tissue-specific DNA methylation after prenatal exposure to arsenic among infants with spina bifida (5R21ES030784-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10217141. Licensed CC0.

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