# Mechanisms of Cervical Epithelial Barrier Protection Against Ascending Infection and Preterm Birth

> **NIH NIH P01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $263,540

## Abstract

Abstract- Mahendroo
Preterm birth (PTB) affects 15 million children world-wide annually contributing significantly to
infant mortality and the potential for lifelong health complications in survivors. An incomplete
understanding of risk factors that lead to preterm birth has limited development of tools for early,
accurate assessment of PTB risk as well as therapies for prevention. Our recent studies have
highlighted the important role that the cervical epithelia play in providing barrier and immune
protection during pregnancy and led to the identification of “cervical epithelial dysfunction” as a
new risk factor for preterm birth. Through pregnancy and parturition, the epithelia must
proliferate, differentiate, and form a junctional and mucosal barrier to protect the reproductive
tract from ascending infection and resulting risk of preterm birth. During pregnancy these
epithelial responsibilities are regulated in part by extracellular matrix cues, specifically by the
increased synthesis of the glycosaminoglycan hyaluronan (HA). Mice lacking HA synthesis in
the cervix display abnormal epithelial differentiation, increased epithelial and mucosal
permeability and increased PTB rates in response to ascending infection. The increase in
cervical hyaluronan during late pregnancy is regulated by increased hyaluronan synthase 2
(Has2) gene expression. The focus of this study is thus to understand i) the mechanism by
which HA participates in cervical epithelial competency, ii) identify downstream transcriptome
targets of HA and iii) understand the transcriptional regulation of Has2 expression in the cervix.
We will test the overall hypothesis that HA’s ability to maintain epithelial cervical barrier function
and immune-protection requires interactions with HA-interacting proteins and mediates
processes involved in epithelial differentiation, barrier function and response to toll-like receptor
signaling.

## Key facts

- **NIH application ID:** 10063455
- **Project number:** 5P01HD087150-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** MALA S. MAHENDROO
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $263,540
- **Award type:** 5
- **Project period:** 2016-12-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063455

## Citation

> US National Institutes of Health, RePORTER application 10063455, Mechanisms of Cervical Epithelial Barrier Protection Against Ascending Infection and Preterm Birth (5P01HD087150-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10063455. Licensed CC0.

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