# Postnatal Complications and Interventions against Halogenated Organics during Pregnancy

> **NIH NIH P42** · UNIVERSITY OF KENTUCKY · 2021 · $197,159

## Abstract

PROJECT SUMMARY
Childhood obesity rates have more than tripled over the last 40 years with 18.5% of children and adolescents
who are now obese. Endocrine-disrupting chemicals, particularly obesogens such as polychlorinated biphenyls
(PCBs) and per- and polyfluoroalkyl substances (PFAS), are contributing to the rapid increases in obesity.
Recent studies indicate that prenatal exposures to PCBs and PFAS contribute to gender-specific obesity
development in children. Both groups of contaminants share a common underlying mechanistic pathway, that
of oxidative stress, and their actions arise from the considerable crosstalk between transcription factors
including nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and the aryl hydrocarbon receptor. Others have
found that treating cells in culture directly with PCBs or PFAS [perfluorooctanesulfonic acid (PFOS) and
perfluorooctanoic acid (PFOA)] influences adipogenesis using human and mouse cells. Importantly, PFOS
induced adipogenesis and glucose uptake by acting through Nrf2. Using a mouse model as part of the
previous round of funding, similar observations were made in that offspring exposed perinatally to PCBs had
significantly worse fat and lean mass profiles compared to offspring born to vehicle-treated dams. Further,
mature offspring born to PCB-exposed dams had impaired glucose tolerance compared to offspring from
vehicle-treated dams. Importantly, a healthy behavioral intervention, maternal voluntary exercise during
pregnancy, improved offspring disease risk associated with in utero PCB exposure. The proposed project will
continue to use an in vivo mouse model as well as transition to human samples in order to examine the
molecular impact of environmental contaminant toxicity during a narrow window of susceptibility. Aim 1 will test
whether voluntary exercise during pregnancy or in the offspring themselves can be used as an intervention
strategy to protect against the long-term metabolic detriments associated with in utero PCB exposure. Aim 2
will elucidate the mechanism of impaired glucose tolerance and altered body composition in offspring born to
PCB-exposed dams (including the use of Nrf2 knockout mice), and will determine how maternal exercise is
protecting offspring from these impairments. Aim 3 will use human cells to identify biomarkers of the specific
harm associated with in utero halogenated organic pollutant exposures and to elucidate the potential
mechanisms that contribute to increased obesity and diabetes risk in exposed infants. Our work will measure
actual contaminant exposure levels in maternal and cord serum, and quantify adipocyte differentiation directly
in cells isolated from the same neonates. Anticipated results are particularly significant in that they highlight
early developmental stages as potential periods of particular vulnerability to program lasting obesity and
diabetes effects of toxic environmental insults.

## Key facts

- **NIH application ID:** 10133664
- **Project number:** 5P42ES007380-23
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Kevin Joseph Pearson
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,159
- **Award type:** 5
- **Project period:** 1997-04-07 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133664

## Citation

> US National Institutes of Health, RePORTER application 10133664, Postnatal Complications and Interventions against Halogenated Organics during Pregnancy (5P42ES007380-23). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10133664. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*