# Maternal-fetal amino acid transfer across placenta in a  mouse model of prenatal alcohol exposure

> **NIH NIH F32** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $67,254

## Abstract

Project Summary/Abstract
Intrauterine growth restriction (IUGR) is a distinctive feature of fetal alcohol spectrum disorder (FASD), which is
a consequence of prenatal alcohol exposure (PAE). Placenta is a specialized organ of pregnancy that supplies
nutrients, such as amino acids (AAs), to the fetus for its growth. AAs are especially important and, when they
are limiting due to reductions in placental AA transport and/or mTOR signaling, fetal growth is impaired and
IUGR ensues. Indeed, placental AA supply is reduced in many pregnancy disorders associated with IUGR, but
whether this contributes to fetal growth deficits in PAE remains unknown. I hypothesize that PAE causes
IUGR, at least in part, by reducing placental AA supply to the fetus, and that this is a consequence of
downregulated placental mTOR signaling, AA transport, and altered AA metabolism. I further propose
that inadequate maternal protein intake, as seen in South African PAE cohorts, worsens this dysfunctional AA
metabolism to exacerbate the growth deficits caused by PAE. To test this, I will feed pregnant mice a protein-
sufficient (NP) or a low protein (LP) diet throughout pregnancy and administer alcohol or isocaloric maltodextrin
during late gestation (GD14.5 – GD17.5), the period during which placenta sharply upregulates AA transport to
accelerate fetal growth. At GD17.5, I will comprehensively assess maternal, placental, and fetal AA
metabolism. Aim 1 performs a comprehensive metabolomics analysis to characterize how PAE decreases AA
supply and metabolic fate along the maternal-placental-fetal axis. Aim 2 performs transcriptomics analysis,
western blotting and immunohistochemistry in placenta to test the hypothesis that downregulation of placental
AA transporters and metabolic genes contributes to the altered AA levels in PAE. Aim 3 performs western
blotting in placenta to test the hypothesis that these changes in AA transport and metabolism are accompanied
by inhibition of placental mTOR pathways, which is a major regulator of AA availability and fetal growth. I
further predict PAE will exacerbate these changes under a LP diet. These studies use cutting-edge techniques
to create a global portrait of how PAE affects placental AA supply and offer novel mechanistic insight into how
PAE and PAE-LP contribute to the IUGR phenotype seen in FASD. These findings lay groundwork for future
studies that examine postnatal neural and metabolic health, the modulatory effect of genetic risk factors, and
the effectiveness of maternal AA supplementation and/or increasing maternal protein intake to improve
outcomes of PAE pregnancies.

## Key facts

- **NIH application ID:** 9976406
- **Project number:** 5F32AA027121-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Sze Ting Kwan
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,254
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-12-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976406

## Citation

> US National Institutes of Health, RePORTER application 9976406, Maternal-fetal amino acid transfer across placenta in a  mouse model of prenatal alcohol exposure (5F32AA027121-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976406. Licensed CC0.

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