# Iron physiology and pathology in pregnancy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $406,908

## Abstract

PROJECT SUMMARY
Adequate iron availability during pregnancy is essential for fetal development and maternal health. Iron deficiency
and its most common manifestation, anemia, are highly prevalent during pregnancy and can have adverse effects on
the mother and the fetus. Recognition of detrimental effects of iron deficiency has led to the policy of universal
iron supplementation in many countries including the US. However, in developed countries, more pregnant
women are iron-replete than iron-deficient. Indiscriminate iron supplementation in this setting may be not only
unnecessary, but may even have harmful effects related to increased oxidative stress or potential adverse
interaction with inflammation. Despite its importance, little is known about the basic physiology of iron regulation
during pregnancy, or how it is altered in complicated pregnancies.
Specific Aim 1. We will define the role of maternal and fetal hepcidin in regulating iron homeostasis during
pregnancy. Our preliminary data in mouse models indicate that maternal iron-regulatory hormone hepcidin must
be suppressed during pregnancy to ensure sufficient iron availability for placental transfer, and that trophoblast
is an important source of the hepcidin-suppressive activity. We will identify the mechanism(s) by which maternal
hepcidin is suppressed in healthy pregnancy; and determine whether maternal hepcidin levels are
inappropriately increased in human inflamed pregnancies to promote maternal iron restriction.
Specific Aim 2. Our preliminary data show that during maternal iron deficiency or excess, placental iron
transporters are regulated to ensure the maintenance of placental iron homeostasis. In response to maternal
iron deficiency in both mice and humans, this mechanism sequesters iron in the placenta at the expense of
providing adequate iron to the fetus, a phenomenon we termed the “selfish placenta”. This has important
implications for understanding the pathogenesis of fetal iron deficiency. We will define the regulatory circuitries
and biological relevance of the selfish placental response in pregnancy.
Specific Aim 3. Our preliminary data in mouse models demonstrate a dramatic adverse interaction between
maternal iron excess and maternal inflammation during pregnancy, targeting placental endothelium, and
resulting in fetal malformations and embryonic lethality. We will define the underlying mechanisms by focusing
on maternal inflammation and pregnancy hormones, as well as placental and fetal inflammation, oxidative stress,
and cell death pathways.
Our proposal will answer fundamental questions about the pathophysiology of maternal and fetal iron regulation
during pregnancy. Long-term, it has the potential to change our approaches to managing iron disorders during
pregnancy.

## Key facts

- **NIH application ID:** 10137092
- **Project number:** 5R01HD096863-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Elizabeta Nemeth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $406,908
- **Award type:** 5
- **Project period:** 2019-06-11 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137092

## Citation

> US National Institutes of Health, RePORTER application 10137092, Iron physiology and pathology in pregnancy (5R01HD096863-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10137092. Licensed CC0.

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