# Paternal preconception phthalates and reproductive health - potential mediation through sperm DNA methylation.

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2021 · $535,084

## Abstract

SUMMARY
Phthalates, a class of endocrine disrupting compounds (EDCs) used in plastics and personal care products, are
ubiquitous environmental contaminants resulting in widespread human exposure. Epidemiologic data implicate
paternal phthalates with adverse reproductive health including poor sperm quality, and more recently, with longer
time to pregnancy − the latter suggests a semen-derived effect. Traditionally, sperm have been considered
vehicles only for the delivery of the paternal genome upon fertilization. However, compelling animal data
demonstrate that environmental conditions in adulthood are embodied within sperm without altering the
underlying DNA sequence, and in turn, these alterations affect offspring health and development. A biological
pathway for this paternal contribution to reproductive success has been shown to include aberrations in sperm
DNA methylation. To date, research in this area has been largely restricted to the effects of nutritional
manipulations in animal models; therefore, relatively little is known about how adult exposures to toxicants affect
epigenetic information in sperm – especially in human populations. We propose that a key to understanding
how adult exposures to phthalates impact reproductive health lies within sperm DNA methylation. This
application capitalizes on the concurrent sample collection from the Sperm Environmental Epigenetics and
Development Study (SEEDS; PI: Richard Pilsner) and the Environmental and Reproductive Health Study
(EARTH; PI Russ Hauser), two independent epidemiologic studies investigating the link between paternal
phthalate exposure and adverse reproductive health among in vitro fertilization (IVF) populations. Moreover, to
address potential generalizability issues stemming from IVF cohorts, we also include in our replication aim,
sperm methylation analyses from samples collected from the Longitudinal Investigation of Fertility and the
Environment (LIFE; PI Germaine Buck Louis) study, a prospective cohort of couples representing the general
population. For our first aim, genome-wide methylation will be analyzed via Illumina’s EPIC array on isolated
sperm remaining after in-vitro fertilization (IVF) from SEEDS. Next, we will determine the relationships of sperm
methylome and on the reproductive outcomes of embryo quality and probability of a live birth in SEEDS. Finally,
after completion of these objectives in SEEDS, we will perform replication studies in sperm samples from EARTH
and LIFE to determine the concordance of findings across the three cohorts. The proposed research is expected
to uncover pathways linking paternal phthalate exposures with adverse reproductive outcomes via sperm DNA
methylation. 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:** 10456477
- **Project number:** 7R01ES028298-04
- **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:** $535,084
- **Award type:** 7
- **Project period:** 2021-09-03 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456477

## Citation

> US National Institutes of Health, RePORTER application 10456477, Paternal preconception phthalates and reproductive health - potential mediation through sperm DNA methylation. (7R01ES028298-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10456477. Licensed CC0.

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