# Flame retardant effects on thyroid hormone regulation at the fetal-maternal interface of the placenta

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $605,906

## Abstract

Project Summary/Abstract
Approximately 12% of infants in the United States are born with low birthweight, or are born too early, which
predisposes them to poorer health outcomes later in life, including impaired neurodevelopment, diabetes,
cardiovascular disease, and chronic respiratory conditions. The causative factors influencing fetal growth, and
how these outcomes vary by fetal sex, are unclear; however, environmental exposures are hypothesized to play
a role. In our prior research, we found that placental tissues associated with male infants accumulated
significantly higher concentrations of brominated flame retardants (BFRs), including polybrominated diphenyl
ethers (PBDEs) and 2,4,6-tribromophenol (TBP), than placenta tissues from female infants, despite no
differences in maternal serum levels based on infant sex. We also found that BFRs concentrate to a significantly
higher degree in fetally-derived placental tissues compared to maternally derived placental tissues (2-10X
higher), in both human tissues and in a rat model, implicating membrane transporters as a mechanism. In the
rat model, thyroid hormone (TH) changes in the placenta were associated with TH changes in the fetuses, in a
sex-specific manner. Several placental membrane transporters, including thyroid hormone transporters, were
also significantly upregulated upon exposure to BFRs and varied by fetal sex. BFRs are endocrine disrupting
chemicals that have been associated with low birth weight and reduced head circumference in several
epidemiological studies. In addition, PBDEs are known to interfere with TH regulation via a number of
mechanisms and have been shown to be substrates for membrane transporters (organic anion-transporter
polypetides) in hepatocytes. Taken together, these preliminary studies suggest placental tissues express
membrane transporters in a fetal-sex dependent manner, which influences BFR accumulation and TH regulation.
Based on these preliminary data, we hypothesize that fetal sex-specific transporter expression in the
placenta influences differential accumulation of BFRs, resulting in sex-specific effects on fetal growth.
To test our hypothesis, we propose to analyze newly collected placental tissues from a prospective cohort in
which we will uniquely isolate and collect maternal and fetal portions of the placenta for analysis. We will couple
this with an in vivo rodent study to examine the mechanism by which BFRs accumulate in the various tissues of
the placenta (i.e. roles of various transporters),and interrogate sex-specific differences in transporter expression
and regulation across gestation. Using the data collected, we will then construct statistical models to evaluate
associations between placental BFR levels and birth outcomes. This innovative study is highly responsive to
the NIH interest in the placenta as a driver of children’s health. Through this project we hope to elucidate the
impact of contaminant exposures on placenta function (e.g. horm...

## Key facts

- **NIH application ID:** 10189595
- **Project number:** 5R01ES031419-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Heather B Patisaul
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $605,906
- **Award type:** 5
- **Project period:** 2020-06-11 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10189595

## Citation

> US National Institutes of Health, RePORTER application 10189595, Flame retardant effects on thyroid hormone regulation at the fetal-maternal interface of the placenta (5R01ES031419-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10189595. Licensed CC0.

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