# Impact of the Placenta Barrier on Fetal Nutrition and Growth Restriction

> **NIH NIH F31** · RUTGERS, THE STATE UNIV OF N.J. · 2020 · $40,516

## Abstract

PROJECT SUMMARY/ABSTRACT
Fetal growth restriction (FGR) is a critical disease that contributes significantly to infant mortality and morbidity.
Although the etiology of FGR is poorly understood, environmental and occupational exposures have been
implicated in its pathogenesis. Measurable levels of the environmental toxicant cadmium (Cd) have been found
in >99% of pregnant women. This widespread exposure is important as Cd has been shown to induce FGR in
rodents and linked to FGR in human epidemiological studies. Cd targets key functions of the placenta that lead
to FGR. Under healthy conditions, the placenta critically regulates nutrient exchange between the maternal and
fetal circulation while at the same time restricts the transfer of toxicants. Efflux pumps, including the breast cancer
resistance protein (human BCRP/rodent Bcrp), are highly expressed on the maternal-facing membrane of
placentas and thus aid in fetal protection by lowering placental (and fetal) xenobiotic concentrations. Our
laboratory has demonstrated that in vitro overexpression of the human BCRP gene lowers intracellular Cd
concentrations and confers resistance against Cd cellular stress and toxicity. However, it is unknown whether
Bcrp in the placenta can regulate Cd toxicity in vivo. To begin to address this question, I have developed a model
of Cd-induced FGR in wild-type mice. Preliminary data reveal a decrease in fetal weights that is accompanied
by a decline in fetal glucose levels following administration of CdCl2 to pregnant mice. These data align with prior
studies suggesting that nutrient transporters are molecular targets of Cd-induced FGR. My central hypothesis is
that placentas with a complete loss or reduction in Bcrp transporter function are at a heightened risk of Cd
accumulation which leads to impaired glucose transfer and utilization and severe fetal growth restriction. I will
utilize two transgenic mouse lines to test this hypothesis: 1) Bcrp-/- mice that have no Bcrp expression and 2)
Bcrp-Q140K mice, a CRISPR model that is orthologous to the human loss-of-function Q141K variant and
recapitulates the reduced functioning of BCRP observed clinically. I anticipate that placentas from Bcrp-/- and
Bcrp-Q140K mice will be more sensitive to Cd accumulation and toxicity compared to wild-type (Bcrp+/+) mice
which will be tested in two specific aims. For this fellowship, I will complete a series of training in rodent and
clinical anatomic pathology of the placenta, coursework and workshops in reproductive biology and toxicology,
and hands-on experimental techniques including ICP/MS and immunohistochemistry. The majority of the training
activities will occur at Rutgers University through the interdisciplinary Joint Graduate Program in Toxicology.
Overall, this proposed research plan will enhance my development into an independent research scientist
through studies completed as part of a Ph.D. dissertation.

## Key facts

- **NIH application ID:** 10066756
- **Project number:** 1F31ES032319-01
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Danielle Kozlosky
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,516
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10066756

## Citation

> US National Institutes of Health, RePORTER application 10066756, Impact of the Placenta Barrier on Fetal Nutrition and Growth Restriction (1F31ES032319-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10066756. Licensed CC0.

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