# Determining how preconception exposure to phthalates impacts sperm function, the epigenome fertility and reproductive outcomes in mice and men

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2021 · $452,638

## Abstract

SUMMARY
Infertility is one of the most common reproductive health disorders affecting 16% of couples in the U.S. Most
concerning are the new meta-analysis data showing that sperm counts among men in developed countries have
declined over 50% in the past four decades. With no sign of reversing this downward trajectory in the most
recent years, we may not only be facing a fertility crisis, but low sperm count has also wider public health
implications including increased risks in morbidity and mortality (3, 4). Given this dramatic decrease in sperm
quality over a short period, genetic influences are likely not attributable, but rather, environmental factors
encountered over the life-course. In particular, phthalates, a class of endocrine disrupting compounds (EDCs)
used in plastics and personal care products, are ubiquitous environmental contaminants resulting in widespread
human exposure. The ViCTER mechanism provides a unique opportunity to enhance cross-disciplinary and
translational research. As such, our research team is poised to determine how paternal preconception
phthalates impacts sperm function, the epigenome and early-life development by leveraging ongoing research
in mice models (R01: ES028214; PI: Dr. Pilsner) and couples undergoing in vitro fertilization (IVF) as part of the
human cohort (Sperm Environmental Epigenetics and Development Study; SEEDS: R01: ES028298; PI: Dr.
Pilsner). We hypothesize that a key to understanding how adult exposures to phthalates affects reproductive
health lies within sperm epigenetics and physiology. Therefore, our ViCTER objectives are to determine the
effects of adult male exposure to phthalates on: 1) small noncoding RNA (sncRNA) in extracellular vesicles (EVs)
(Dr. Pilsner); 2) sperm histone methylation (Dr. Kimmins); and 3) sperm capacitation, IVF and embryo
development (Dr. Visconti). For our first aim, we will examine the associations of paternal phthalate exposure on
sncRNA expression from extracellular vesicles (EVs) of mice and men. Next, we will examine the effect of adult
male exposure to phthalates on histone methylation in sperm from mice and men. Finally, we will determine the
effect of adult mouse exposure to DEHP, DBP and its mixture on sperm capacitation, acrosome reaction and
subsequent embryo development. The proposed research is expected to uncover pathways linking paternal
phthalate exposures with adverse reproductive outcomes via sperm physiology and epigenetics.
Characterization of potential intermediate pathways between the exposure and outcome continuum is of
significant importance because it will inform avenues of translational research for the development of novel
approaches to treat and prevent adverse reproductive health.

## Key facts

- **NIH application ID:** 10459891
- **Project number:** 7R01ES030942-03
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** J. Richard Pilsner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $452,638
- **Award type:** 7
- **Project period:** 2021-09-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459891

## Citation

> US National Institutes of Health, RePORTER application 10459891, Determining how preconception exposure to phthalates impacts sperm function, the epigenome fertility and reproductive outcomes in mice and men (7R01ES030942-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10459891. Licensed CC0.

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