# Imprinted Gene Regulation by in utero Lead Exposure in Mice

> **NIH NIH K01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $154,309

## Abstract

PROJECT SUMMARY
The objective of this study is to determine epigenetic mechanisms that impact genomic imprinting upon in utero
exposure of mice to human-relevant levels of lead (Pb). Pb is an infamous environmental exposure to human
populations in the US and around the world, due in part to its neurotoxic effects. Pb exposure during early
development has been linked to adverse health outcomes later in life. Preliminary data generated for this grant
indicates that in utero and perinatal Pb exposure increases placenta/embryo size, and alters the DNA
methylation of imprinted genes, respectively. However, the molecular mechanisms by which Pb exposure
reprograms genomic imprinting during early gestation remain largely unknown. Imprinted genes are
epigenetically regulated in a parent-of-origin specific manner with their mono-allelic expression driving critical
periods of development. Known mechanisms of genomic imprinting include the 1) long non-coding RNA
(lncRNA) and 2) insulator models, each of which program allele-specific regulation of imprinting control
regions. Although dysfunctional genomic imprinting is implicated in several human diseases, the mechanisms
leading to toxicant-induced imprinting dysregulation by the two models remain poorly understood. Using an
established Pb exposure mouse model, this study seeks to determine in utero mechanisms that impact
genomic imprinting and health effects from altered epigenetic reprogramming. Thus, female animals exposed
to Pb two weeks prior to mating through 13-14 days post-conception will be used in the following Aims: 1)
Determine fetal sex-specific imprinting dysregulation associated with in utero Pb exposure in mouse placenta,
2) Assess allele- and sex-specific mechanisms of in utero Pb exposure regulating genomic imprinting in the
brain. Pb-exposed animals will be compared against controls to investigate genomic imprinting mechanisms in
the lncRNA and insulator models by characterizing sex-, tissue-, and developmental stage-specific imprinted
gene dysregulation via phenotypic, gene expression, DNA methylation, and immunohistochemical analyses.
This study will reveal Pb-associated lncRNA mechanisms that inform the current epigenetic reprogramming by
fetal sex. The University of Michigan provides an ideal environment to conduct the proposed research in
collaboration with multiple core facilities outlined herein. The candidate will receive mentorship from a
multidisciplinary team of experts to: 1) Gain proficiency in computational and statistical skills required for data
analysis; 2) Acquire expertise in developmental toxicological research and mechanistic investigation; and 3)
Build skills critical for leadership, teaching and mentoring, laboratory management, and grantsmanship. The
proposed study will address fundamental knowledge gaps of genomic imprinting in the field to inform potential
Pb-induced disease interventions. The training and research goals established in this K01 proposal constitute
...

## Key facts

- **NIH application ID:** 10805705
- **Project number:** 1K01ES035064-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Bambarendage Pinithi Upekka Perera
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $154,309
- **Award type:** 1
- **Project period:** 2024-02-13 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805705

## Citation

> US National Institutes of Health, RePORTER application 10805705, Imprinted Gene Regulation by in utero Lead Exposure in Mice (1K01ES035064-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10805705. Licensed CC0.

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