# Project 1 - Lechner

> **NIH NIH P20** · WOMEN AND INFANTS HOSPITAL-RHODE ISLAND · 2021 · $338,085

## Abstract

PROJECT SUMMARY/ABSTRACT
There is a key gap in knowledge with respect to mechanisms leading to preterm premature rupture of fetal
membranes (PPROM). Continued existence of this gap represents an important problem because, until it is
filled, the development of successful strategies for the prevention and treatment of PPROM will remain
elusive. The long-term goal of this proposal is to reduce the incidence of PPROM-induced preterm birth. The
objective here is to determine the extracellular matrix mechanisms that lead to PPROM. The central
hypothesis for this proposal is that the extracellular matrix proteoglycans biglycan and decorin contribute to
the maintenance of intact fetal membranes throughout gestation. This hypothesis is based on preliminary data
that support a role for these mechanisms in maintenance of pregnancy. Preliminary studies show that the
absence of biglycan and decorin in mice leads to preterm birth, abnormal fetal membrane morphology and
altered signaling pathways, and that the phenotype is enhanced on exposure to inflammation. Furthermore,
human fetal membranes with PPROM display decorin dysregulation. The rationale for the proposed research
is that completion of these aims will define key biglycan- and decorin-dependent mechanisms that contribute
to the integrity of fetal membranes, resulting in new and innovative strategies for the prevention and treatment
of PPROM. Guided by strong preliminary data, this hypothesis will be tested by pursuing three specific aims:
1) Identify the contributions of the proteoglycans biglycan and decorin to successful gestation using mice
deficient in these proteoglycans; 2) Identify the mechanisms by which the extracellular matrix contributes to
the structural integrity of the fetal membranes throughout gestation in the biglycan/decorin knockout mouse;
and 3) Elucidate the status of the extracellular matrix in fetal membranes after PPROM in humans. Under the
first aim, a maternal-fetal divergent genotype approach will be used to assess the extracellular matrix
contribution to fetal membrane stability. For the second aim, fetal membrane biomechanical testing and
recombinant biglycan rescue testing will be performed. For the third aim, human fetal membrane proteoglycan
expression will be assessed. Each approach has been established as feasible in the applicants' hands. The
contribution of the proposed research is expected to be the identification of novel biglycan- and decorin-
dependent mechanisms that contribute to protection against PPROM. The proposed research is innovative
because it represents a new and substantive departure from the status quo, namely the approach of
extracellular matrix proteoglycan contribution to the stability of the fetal membranes using knockout fetal
membrane mechanical testing, proteoglycan therapy and embryo transfer. The proposed research is
significant because it is expected to vertically advance our understanding of extracellular matrix contribution to
the stabi...

## Key facts

- **NIH application ID:** 10145032
- **Project number:** 5P20GM121298-05
- **Recipient organization:** WOMEN AND INFANTS HOSPITAL-RHODE ISLAND
- **Principal Investigator:** Beatrice Elizabeth Lechner
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $338,085
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145032

## Citation

> US National Institutes of Health, RePORTER application 10145032, Project 1 - Lechner (5P20GM121298-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10145032. Licensed CC0.

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