# Placental Responses to Environmental Chemicals - Diversity Supplement 2

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2021 · $139,538

## Abstract

PARENT PROJECT ABSTRACT
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:** 10360791
- **Project number:** 3R01ES029275-04S1
- **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:** 2021
- **Award amount:** $139,538
- **Award type:** 3
- **Project period:** 2018-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10360791

## Citation

> US National Institutes of Health, RePORTER application 10360791, Placental Responses to Environmental Chemicals - Diversity Supplement 2 (3R01ES029275-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10360791. Licensed CC0.

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