# Environmentally Relevant Phthalate Exposures and Ovarian Function

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $456,527

## Abstract

PROJECT SUMMARY/ABSTRACT
Approximately 6.7 million American women are unable to become pregnant or carry a baby to term. Any
environmental exposure that causes damage to the ovary has the potential to cause infertility in women.
Phthalates represent a significant concern for human fertility because they have been associated with early
menopause, decreased hormone levels, and early pregnancy loss in women. Studies in animal models
suggest that phthalates may impair fertility through their ability to disrupt ovarian function. Ovarian follicles, the
functional units of the ovary, exist in various stages of development that range from the most immature
primordial follicles to the large pre-ovulatory follicles, the stage at which they capable of sustaining hormone
production and ovulating of health oocyte. Survival and successful transition to the large pre-ovulatory follicle
stage depends on the positive actions of various factors including follicle-stimulating hormone (FSH), insulin-
like growth factor 1 (IGF1), and 17β-estradiol (E2) which form a pro-survival network critical for the
maintenance of fertility. There is, therefore, a critical need to identify the interactions between phthalates and
these pathways to improve our ability to characterize the risk posed by phthalates and identify biomarkers and
pharmaceutical targets to screen and treat infertility due to endocrine disruption. The main objective of this
proposal, is to use environmentally relevant exposures to phthalates to test the central hypothesis that
phthalates target the FSH-IGF1-E2 system, compromise follicle-dependent processes, and cause premature
ovarian failure by increasing the rate of ovarian follicle loss in mice. To achieve our goal, we propose to use
three model phthalates (DBP, DEHP, BBP) to (1) determine whether environmentally relevant exposures to
phthalates alter follicular dynamics and disrupt FSH-IGF1-E2 signaling, (2) determine whether environmentally
relevant exposures to phthalates cause follicular death by increasing apoptosis, and (3) identify the
phenotypes resulting from environmentally relevant exposures to phthalates on processes that rely on healthy
ovarian follicles. These studies will use environmentally relevant exposures to identify which signaling
pathways, follicle types and individual ovarian cell compartments are most sensitive to phthalates and establish
the phenotypes that result from these relevant exposures. By doing so, this work will facilitate the
characterization of the risks of phthalate exposure and provide leads for potential biomarkers and therapeutic
targets to detect and treat phthalate-induced reproductive toxicity. Our team is well-positioned to successfully
complete the proposed work based on experience and institutional resources as detailed in the application.

## Key facts

- **NIH application ID:** 9927631
- **Project number:** 5R01ES026998-04
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Zelieann Rivera Craig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $456,527
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927631

## Citation

> US National Institutes of Health, RePORTER application 9927631, Environmentally Relevant Phthalate Exposures and Ovarian Function (5R01ES026998-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9927631. Licensed CC0.

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