# Cellular mechanisms in immune-driven placental injury

> **NIH NIH F31** · STANFORD UNIVERSITY · 2020 · $38,497

## Abstract

PROJECT SUMMARY
Infections, allergy or asthma during the first two trimesters of pregnancy can increase miscarriage, preterm birth,
and the offspring’s risk of poor developmental outcomes. These gestational risks are largely mediated by the
placenta, a critical interface comprised of maternal and fetal tissues and mediator of immune responses between
mother and fetus. Infections and other immune events during pregnancy contribute to risk but very little is known
about placental immune cell profiles and their precise responses to maternal immune perturbations. Without this
knowledge, developing therapies to reduce the broad spectrum of gestational risks and impacts on offspring will
be greatly inhibited. In mice, early gestational immune challenges also negatively impact fetal health and
development, allowing us to use the maternal immune activation mouse model. Pregnant mice given an immune
challenge that mimics a bacterial infection before embryonic day 13.5 (E13.5) experience pronounced fetal loss
and placental damage, but become resistant after E13.5. In this model, the immune challenge leads to placental
hemorrhage. Preliminary data have implicated several immune cell types and these observations led to the
central hypothesis that maternal immune activation in early pregnancy causes placental cytokine release and
immune cell recruitment, resulting in placental damage. The project involves two specific aims: 1) Determining if
differential recruitment of maternal immune cells to the placenta mediates injury, and 2) Determining how the
maternal immune response varies across gestation. Under the first aim, a mass cytometry panel developed by
the Palmer lab will be used to study the immune cell subsets and immune function in the placenta at baseline
and following immune challenge at vulnerable (E12.5) and resistant (E14.5) times. Immune cell recruitment to
the placenta will be inhibited using chemokine receptor knockout mice to determine whether immune cell
infiltration is necessary for placental injury. Under the second aim, immune cell subsets and immune function
will be measured in maternal blood, thymus, lymph nodes, and uterine horn at baseline and following immune
challenge at vulnerable and resistant times. The findings from this study will show how immune challenges in
early pregnancy alter immune cell behavior systemically in the mother and locally in the placenta and will define
the mechanisms that underlie placental and fetal vulnerability to the maternal immune response in early
pregnancy and relative resilience in late pregnancy. The information obtained from this project will allow us to
identify therapeutic targets that prevent placental damage and reduce pregnancy complications.

## Key facts

- **NIH application ID:** 9993994
- **Project number:** 5F31HD095569-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Amber Arthur
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,497
- **Award type:** 5
- **Project period:** 2018-09-02 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993994

## Citation

> US National Institutes of Health, RePORTER application 9993994, Cellular mechanisms in immune-driven placental injury (5F31HD095569-03). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/9993994. Licensed CC0.

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