# Adrenomedullin Signaling at the Maternal-Fetal Interface

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $414,865

## Abstract

Project Abstract
 Adrenomedullin (AM) is a multifunctional peptide that is involved in a variety of biological
processes, including embryonic development, angiogenesis, cardio-protection, and innate
immunity. Maternal plasma levels of AM rise substantially during a normal pregnancy, but
abnormally low levels are often associated with a variety of pregnancy complications including
preeclampsia, fetal growth restriction, gestational diabetes and spontaneous abortion. Using
genetically engineered mouse models, our laboratory was the first to demonstrate that
haploinsufficiency for maternal AM causes a multitude of reproductive defects associated with
abnormal implantation and fetal growth restriction. More recently, we extended these findings to
humans by identifying the first loss-of-function mutation in the AM G protein-coupled receptor
CALCRL, associated with hydrops fetalis, placental edema and maternal subfertility. Collectively
our prior studies have defined the ways in which dosage of AM peptide and receptors can impact
reproductive success, in animal models and in humans. Therefore, in this competitive renewal we
are uniquely positioned to extend on our previous work by asking the overarching “bench-to-
bedside” question of " How does AM signaling affect its target cells during implantation and
placentation and whether extrinsic factors can alter levels of AM to exert physiological effects on
pregnancy outcomes?" The focus of our studies places AM signaling as a cornerstone for
elucidating fundamental questions related to pinopode formation (Aim 1), growth and remodeling
of placental/decidual vasculature (Aim 2) and the roles of extrinsic environmental factors on
reproductive outcomes (Aim 3). Using sophisticated genetic mouse models and in vitro
pharmacological and cell biological assays, we intend to further our basic understanding of
molecules and processes that govern maternal-to-fetal communication in the placenta and have
the potential of providing new clinical therapeutic targets for the amelioration of complications of
pregnancy.

## Key facts

- **NIH application ID:** 10828375
- **Project number:** 5R01HD060860-12
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Kathleen M Caron
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $414,865
- **Award type:** 5
- **Project period:** 2009-04-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828375

## Citation

> US National Institutes of Health, RePORTER application 10828375, Adrenomedullin Signaling at the Maternal-Fetal Interface (5R01HD060860-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10828375. Licensed CC0.

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