# Innate Immune Mechanisms at the Maternal-Fetal Interface in Normal and Superovulatory Pregnancy

> **NIH NIH R01** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2022 · $766,689

## Abstract

Project Summary/Abstract
Placental insufficiency underlies many pregnancy disorders, including preeclampsia (PE), intrauterine growth
restriction (IUGR) and recurrent pregnancy loss (RPL). Collectively, these disorders have costly, widespread,
and sometimes long term, health consequences for the mother and/or child. Immune cell populations at the
maternal-fetal interface, including uterine natural killer cells (uNKs) and uterine macrophages (uMacs), mediate
angiogenesis and other key events in decidualization, placentation, and progression of pregnancy.
Dysregulated inflammatory responses during decidualization or placentation have been linked to PE, IUGR,
and RPL. Moreover, a growing number of births in the US are achieved using controlled ovarian stimulation
(“superovulation”) protocols for in vitro fertilization (IVF), which is associated with dysregulated uterine immune
cell function and increased risk of pregnancy complications due to placental dysfunction.
 The molecular mechanisms that regulate immune cell function at the maternal-fetal interface are poorly
understood. Recent studies have highlighted critical roles for the IL-1 family cytokine, IL-33, in pregnancy, and
aberrant maternal IL-33 signaling has been linked to RPL and PE in humans. Our preliminary data reveal
numerous IL-33-expressing cells, including many IL-33+ uterine epithlelial cells, in the murine uterus at key
stages of pregnancy. These IL-33+ cells are located in immune cell-rich regions heavily populated by uNKs
and uMacs. Although IL-33 regulates key aspects of NK and Mac function in other tissues, its specific effects
on uNKs and uMacs remains poorly understood. We hypothesize that IL-33 signaling supports decidualization
and placentation by promoting uNK and uMac-mediated angiogenesis and tissue remodeling during
pregnancy. Guided by this hypothesis, our proposed studies aim to:
(1) Define the role of IL-33 signaling in pregnancy progression. We will utilize mice that lack IL-33 globally
or in uterine epithelial cells, or mice in which IL-33 is neutralized at key stages of gestation, to define the role of
IL-33 in decidualization, placental formation and placental function during pregnancy.
(2) Determine the effects of IL-33 signaling on NK and Mac function at the maternal-fetal interface. We
will use complementary in vitro approaches and in vivo studies in IL-33-deficient mice to determine how IL-33
signaling regulates the angiogenic and tissue remodeling activities of uNKs and uMacs during pregnancy.
(3) Determine the impact of superovulation (SO) on uNK and uMac function. We will use mouse models
of SO, in combination with studies on primary human endometrial samples from women undergoing SO for
IVF, to investigate the impact of SO on IL-33-dependent and –independent uNK and uMac effector functions.

## Key facts

- **NIH application ID:** 10447103
- **Project number:** 7R01AI148695-04
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** Aimee Melissa Beaulieu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $766,689
- **Award type:** 7
- **Project period:** 2019-08-21 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447103

## Citation

> US National Institutes of Health, RePORTER application 10447103, Innate Immune Mechanisms at the Maternal-Fetal Interface in Normal and Superovulatory Pregnancy (7R01AI148695-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10447103. Licensed CC0.

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