# Preconception phthalate exposure and offspring outcomes

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $441,000

## Abstract

Endocrine disruptors (EDs) are a group of molecules capable of altering normal endocrine
function in animals and humans. We and others have demonstrated that in utero exposure to
EDs causes obesity and abnormal glucose homeostasis in the offspring. Phthalates are an
important group of EDs that are used in a diverse range of industrial applications leading to
common exposure risk in humans. One major phthalate is di-(2-ethylhexyl)-phthalate (DEHP), a
widely used compound for which dietary exposure (food processing, packaging) likely
represents the main source of contamination for the general population. Both human and animal
models show a link between phthalate exposure and the development of obesity and the
metabolic syndrome. Similar to these studies, our preliminary data show that DEHP exposure
through the diet in physiologically relevant doses prior to and during pregnancy and lactation
alters DNA methylation in fetal liver, increases body weight in adult offspring in a sex-specific
manner. It is becoming increasingly evident that the periconceptional stage also represents a
window of susceptibility to environmental exposures on the offspring. While the mechanisms
responsible for the transfer of metabolic memory from the oocyte to the offspring remain to be
elucidated, 2 plausible possibilities are epigenetic dysregulation and abnormal mitochondria.
Further, we and others have shown that epigenetic changes and abnormal mitochondrial
function in key organs such as the liver, ß-cell and muscle have been linked to development of
obesity and diabetes. Thus, we hypothesize that a preconception exposure to DEHP, similar to
a gestational exposure, results in an abnormal metabolic phenotype in the offspring by altering
either the epigenetic profile and or mitochondrial function in the oocyte. Thus we propose the
following specific aims: Aim 1 will determine whether a preconception exposure to biologically
relevant doses of DEHP results in a similar offspring phenotype as a gestational exposure. Aim
2 will determine the molecular and cellular mechanisms by which the two different exposure
windows result in a similar or different metabolic phenotype in the offspring. We will profile the
transcriptome by RNA-seq and the epigenome by ATACseq and bisulfite-seq in the oocyte and
key tissues in the offspring. We will then determine the effects of DEHP on key aspects of
mitochondrial function such as respiration, ATP, ROS, and morphology. The proof of the
principle of preconception programming by environmental contaminants may change our
awareness of critical assessment of the risk of such compounds.

## Key facts

- **NIH application ID:** 10246409
- **Project number:** 5R01ES028206-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** MARISA S. BARTOLOMEI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $441,000
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246409

## Citation

> US National Institutes of Health, RePORTER application 10246409, Preconception phthalate exposure and offspring outcomes (5R01ES028206-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10246409. Licensed CC0.

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