# Reproductive Phenotype of Adrenomedullin2 (ADM2) knockout mice

> **NIH NIH R03** · BAYLOR COLLEGE OF MEDICINE · 2022 · $80,000

## Abstract

Abstract
Adrenomedullin2 (ADM2) is a novel hypotensive peptide that promotes trophoblast invasion. Lower ADM2
levels are associated with pregnancy complications such as spontaneous abortion, fetal growth restriction
(FGR) and preeclampsia (PE).Pilot data shows that ablation of ADM2 gene causes PE-like manifestations
such as elevated blood pressure (BP) and increased serum levels of soluble fms-like tyrosine kinase-1 (sFLT-
1), along with early parturition and increased pup mortality in pregnant ADM2 knockout (ADM-/-) mice. This
data strongly supports our published studies showing: 1) Higher placental and serum levels of ADM2 during
the invasive phase of placental development in human pregnancy, 2) ADM2 mediated increases in the invasive
capacity of 1st trimester extravillous trophoblast cells (EVCTs) in human pregnancy, 3) decreased serum and
placental ADM2 levels in PE and decreased ADM2 in amniotic fluid of pregnant women in 2nd trimester who
develop PE. Further, while impaired nitric oxide (NO) production and elevated synthesis and secretion of
placental sFLT-1 is reported to cause endothelial dysfunction in PE, blocking ADM2 in rat pregnancy decrease
placental NO/ matrix metallo-proteinase (MMP) system accompanied with FGR and impaired placental
vasculature. In addition, knockdown of ADM2 in trophoblast cells decreases the expression of MMP2, MMP-9
and eNOS mRNA. Therefore, based on above mentioned reports and pilot data, our central hypothesis is that
“Global ablation of ADM2 results in pregnancy complications mimicking preeclampsia in human and that, it
functions through NO/MMP system “. This hypothesis will be tested using three specific aims. Specific Aim-1:
Assess the effect of ADM2 ablation on feto-placental growth, circulatory levels of nitric oxide, 17β-estradiol,
progesterone and blood pressure regulation during pregnancy; and identify if NO supplementation can rescue
early parturition and increased pup mortality, in ADM2-/- animals, Specific Aim-2: Determine if ablation of
ADM2 in mice advances uterine contractility and potentiates uterine contractile responses to stimuli such as
oxytocin and prostaglandin-F2α, through increase in their receptor expression and, Specific Aim-3: Identify 1)
downstream signaling mechanism involved in the invasive function of ADM2 in EVCTs and, 2) assess if ADM2
supplementation can increase the invasive capacity of EVCTs from PE, which are reported to exhibit less
invasive phenotype compared to those from normal pregnancy.
 Since the majority of studies in humans are limited by their inherent correlative nature, our proposed
approach will allow us to characterize the endogenous functions of ADM2 in pregnancy in a series of
mechanistic experiments and its potential role in the pathophysiology of PE. These studies could potentially fill
the gaps in the knowledge of mediators of placental functions that may hold great potential for the design and
implementation of an effective prevention/treatment for path...

## Key facts

- **NIH application ID:** 10301366
- **Project number:** 5R03HD098438-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Madhu Lata S. Chauhan
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $80,000
- **Award type:** 5
- **Project period:** 2020-11-12 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10301366

## Citation

> US National Institutes of Health, RePORTER application 10301366, Reproductive Phenotype of Adrenomedullin2 (ADM2) knockout mice (5R03HD098438-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10301366. Licensed CC0.

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