# Mechanisms of developmental and reproductive toxicity from preconceptional BaP exposure

> **NIH NIH R21** · UNIVERSITY OF MISSISSIPPI · 2020 · $181,468

## Abstract

Mechanisms of developmental and reproductive toxicity from preconceptional BaP
exposure
The University of Mississippi
ABSTRACT
Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that represents a class of ubiquitous
environmental contaminants derived from the incomplete combustion of carbon. Human exposures to PAHs
are associated with developmental and reproductive deficits. The goal of this R21 project is to characterize the
transcriptomic and epigenetic changes associated with preconceptional exposure to BaP. Specifically, we will
determine the role of the aryl hydrocarbon receptor (AhR) in BaP-induced multigenerational phenotypes. The
AhR is a ligand activated transcription factor that is critical in regulation of diverse cellular functions from
xenobiotic metabolism to cellular proliferation and differentiation. AhR activation is recognized in etiologies
for birth defects and embryo lethality. Our central hypothesis is that persistent toxicity of BaP is dependent on
the BaP-AhR interaction and AhR activation affects transcriptomic and DNA methylation profiles. To test this
hypothesis, we will use zebrafish, an established model in developmental toxicology, particularly in
developmental origins of adult health and disease (DOHaD) research. We have reported that multigenerational
developmental impacts are present in F1 and F2 offspring after parental only BaP exposure. Our study design
will involve dietary BaP exposures to either wild type or AhR null F0 parents and will allow us to measure the
relationships between global gene expression and epigenetic changes in DNA methylation status in F0 and F1
germ cells and F1 embryos. Differentially expressed and methylated genes will be evaluated to explain the AhR-
and BaP-mediated adverse outcomes in development and reproduction. Comparing AhR null and wild type
constitutive gene expression and methylation status in germ cells and embryos could also reveal currently
unknown roles of AhR in normal physiology. A cross-over mating protocol will reveal the sex-dependence in
molecular and phenotypic endpoints. This research will address the significant knowledge gap that exists
related to mechanisms underlying BaP’s latent toxicity following preconceptional exposure. The proposed
comprehensive –omics approach is consistent with the R21 exploratory, high-risk, high-reward funding
mechanism. Importantly, this study will address the NIEHS emphasis areas of environmental epigenetics and
developmental basis of adult disease; areas currently lacking appropriate consideration in risk assessment.

## Key facts

- **NIH application ID:** 9833524
- **Project number:** 5R21ES030154-02
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI
- **Principal Investigator:** KRISTINE L WILLETT
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $181,468
- **Award type:** 5
- **Project period:** 2018-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9833524

## Citation

> US National Institutes of Health, RePORTER application 9833524, Mechanisms of developmental and reproductive toxicity from preconceptional BaP exposure (5R21ES030154-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9833524. Licensed CC0.

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