# Mechanisms by which steroid hormones modulate cervical extracellular matrix structure and function during pregnancy and provide therapeutic protection against preterm birth

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $354,323

## Abstract

ABSTRACT
On an annual basis 3.3 million babies will die worldwide due to complications in pregnancy that leads to
preterm birth (PTB) or stillbirths. Despite much investigation, the current understanding of the mechanisms of
term and preterm parturition remains limited, the identification of risk factors is incomplete, and preventative
therapies are few. Supplemental progesterone (P) therapy in women with a singleton pregnancy and a
previous history of PTB is currently the standard of care to prevent PTB in the United States. Yet, our
mechanistic understanding of its mode of action is absent. Cervical remodeling, the process by which the
cervix transforms from a closed rigid structure to a compliant structure that can open to allow safe passage of
the fetus, is a key and essential feature of normal parturition. In human and mice, this process begins in early
pregnancy. Thus improved understanding of this mechanism has the potential to inform new early preventative
therapies and provide mechanistic insight into current therapies. Based on novel findings in mice lacking the
proteoglycan, decorin, we provide evidence that 1) a dysfunctional cervical extracellular matrix (ECM) leads to
cervical insufficiency, 2) cervical mechanical dysfunction results from defects in both collagen and elastic fiber
assembly and 3) structural organization of the cervical ECM in pregnancy is under exquisite control by
progesterone and estrogen. The goal of the current study is to identify the P and E regulated transcriptional
networks that regulate ECM structure, protein turnover and mechanical function and to explore the mechanism
by which decorin ensures cervical competency in the nonpregnant and early pregnant cervix. Finally we will
use mice deficient in the proteoglycans decorin and biglycan to test the hypothesis that P supplementation can
repair mechanical function of the cervix and thus provide one mechanism by which P supplementation is
beneficial in reducing risk of PTB in women with a previous PTB. Collectively the proposed studies, based on
compelling preliminary data, has the potential to both expand our understanding of basic mechanisms in
parturition as well as expand the possibilities for clinical intervention in PTB.

## Key facts

- **NIH application ID:** 9982389
- **Project number:** 5R01HD088481-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** MALA S. MAHENDROO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $354,323
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982389

## Citation

> US National Institutes of Health, RePORTER application 9982389, Mechanisms by which steroid hormones modulate cervical extracellular matrix structure and function during pregnancy and provide therapeutic protection against preterm birth (5R01HD088481-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982389. Licensed CC0.

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