# Placental Responses to Environmental Chemicals

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2020 · $706,477

## Abstract

PROJECT SUMMARY
Environmental exposures during gestation can alter early growth trajectories and increase the risk of
developing chronic diseases including diabetes, hypertension, and obesity. Among the exposures of greatest
concern is cadmium, a metal that is extensively used in the electronics industry. Cadmium is a high priority
toxicant with adverse clinical effects reported in both adults and children. During pregnancy, cadmium
accumulates in the placenta where it induces cellular stress, interferes with hormone production, and limits the
transfer of nutrients from mother to child. This leads to smaller offspring size at birth in humans and animal
models. Identifying cellular mechanisms that can modify cadmium’s toxicity in the placenta are key to
preventing the adverse outcomes associated with fetal growth restriction due to cadmium, a chemical that will
persist in our environment for the foreseeable future. One mechanism that reduces placental accumulation of
environmental chemicals is active transport by efflux proteins. The breast cancer resistance protein
(BCRP/ABCG2), an efflux transporter highly expressed on syncytiotrophoblasts, plays a critical role in
restricting the placental accumulation of chemicals. The overarching hypothesis of this research is that BCRP
is a critical mechanism limiting placental exposure to cadmium; when BCRP function is reduced, cadmium’s
toxic effects on the placenta are enhanced, resulting in fetal growth restriction. This hypothesis will be tested in
three specific aims using innovative and translational experimental approaches. The multidisciplinary research
team includes a biochemical toxicologist, biomedical engineer, and an epidemiologist. To study the ability of
BCRP to prevent cadmium-induced placental toxicity, a complement of culture models, including a novel
‘Placenta-on-a-Chip’ as well as term villous explants from healthy pregnancies will be used. To test the in vivo
ability of BCRP to prevent cadmium-induced fetal growth restriction, transgenic pregnant mice will be treated
with cadmium chloride and evaluated for placental toxicity and fetal growth restriction. The UPSIDE cohort of
310 healthy, pregnant women will be examined for prenatal exposure to metals, including cadmium, and
transporter genomics/proteomics in relation to 3D placental morphology and infant growth outcomes.
Ultimately, this line of research will inform the scientific community regarding the ability of placental
transporters to protect the fetus from environmental chemical-induced developmental toxicities.

## Key facts

- **NIH application ID:** 9914832
- **Project number:** 5R01ES029275-03
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Lauren M Aleksunes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $706,477
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9914832

## Citation

> US National Institutes of Health, RePORTER application 9914832, Placental Responses to Environmental Chemicals (5R01ES029275-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9914832. Licensed CC0.

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