# Defining the role of in utero estrogenic endocrine disruption on mammary gland stiffness and breast cancer risk

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $346,031

## Abstract

PROJECT SUMMARY / ABSTRACT
Estrogenic endocrine disrupting compounds (EDCs) are ubiquitous in pesticides and other industrial
products where they remain active in the environment for extended periods. Daughters of women who were
exposed prenatally to the estrogenic EDC diethystilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT)
exhibit an increased risk of breast cancers. Despite a link between EDC exposure and cancer risk the
detailed mechanism(s) that ultimately drive tumorigenesis remains largely unknown. This lack of
understanding limits the ability to accurately determine the individual and population risk of estrogenic EDC
exposures. The goal of this proposal is to determine the mechanism(s) that links EDC exposure to cancer
and to provide biological markers capable of evaluating EDC exposure risk.
We have identified a number of EDC-driven reprogramming events within the mammary gland stroma.
These events include increased collagen deposition that results in increased mammary gland stiffness and
decreased permeability of the extracellular matrix (ECM). Similar stromal tissue changes have been shown
to increase cancer susceptibility in animal models and appear to provide a biological connection to EDC-
driven tumorigenesis. It is our overarching hypothesis that estrogenic EDCs alter the homeostatic
signaling within the mammary gland leading to ECM changes that ultimately drive breast cancer. We
propose to test this hypothesis using a well-defined mouse model system with the following Specific Aims: 1)
Characterize the estrogenic EDC-induced mechanism(s) that contribute to breast stromal molecular and
tissue alterations. 2) Evaluate the contribution of estrogenic EDC-induced stromal alterations to breast
cancer risk. These studies will answer several key questions in the field including how the estrogenic activity
of EDCs impact stromal alterations, how stromal alterations alter tissue homeostatic signaling during
mammary gland development and determine the epigenetic reprogramming events within stromal fibroblasts
that propagate an EDC exposure from the womb through adulthood. We expect that this analysis will provide
a strong foundation for understanding how environmental EDCs drive tumorigenesis as well as provide
potential biomarkers and therapeutic targets for EDC exposure.

## Key facts

- **NIH application ID:** 10457430
- **Project number:** 5R01ES032026-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Craig J Burd
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $346,031
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457430

## Citation

> US National Institutes of Health, RePORTER application 10457430, Defining the role of in utero estrogenic endocrine disruption on mammary gland stiffness and breast cancer risk (5R01ES032026-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10457430. Licensed CC0.

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