# Molecular and Genomic Mechanisms in the Biology of Pregnancy and Parturition

> **NIH NIH P01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $1,343,013

## Abstract

PROJECT SUMMARY/ABSTRACT
In this new program project, we will utilize comprehensive global genomic approaches (RNA sequencing [RNA-seq], global run-on sequencing [GRO-seq], and chromatin immunoprecipitation sequencing [ChIP-seq]) to
understand the biological mechanisms for term and preterm birth. This application is timely, because of the
huge advances in genomic technologies combined with cutting-edge computational tools, which have dramatically advanced our understanding of signal-regulated gene transcription in a wide variety of biological systems.
The global views generated by these assays provide a uniquely informative biological perspective that cannot
be achieved by analyzing one or even a few genes at a time. We propose to utilize these state-of-the-art
techniques to develop an in-depth understanding of the genomic and epigenomic mechanisms that underlie
the regulation of myometrial quiescence-contractility, cervical competency-dilation, and that maintain barrier
function of the cervix to protect the pregnancy against invading microorganisms and prevent prematurity. The
P01 includes four interrelated projects: Project 1: Epigenetic Regulation of Myometrial Contractility in
Pregnancy and Labor (Carole R. Mendelson); Project 2: Functional Roles of Estrogen Receptor α Acetylation
in the Uterus (W. Lee Kraus); Project 3: Genomic Consequences of Estrogen Receptor Activation in the Cervix
(R. Ann Word); Project 4: Mechanisms of Cervical Epithelial Barrier Protection Against Ascending Infection and
Preterm Birth (Mala S. Mahendroo), supported by three cores: Administrative Core (Mendelson); Genomics
and Computational Core (Kraus); Human Tissue and Biological Fluid Acquisition Laboratory Core (Word). The
goals of these projects are: Project 1 - to define the genes and mechanisms that underlie the actions of
progesterone (P4), via progesterone receptor isoforms, PR-A and PR-B, on inflammatory and `contractile' gene
expression, and to characterize the chromatin modifications that mediate myometrial quiescence and
accompany enhanced contractile gene expression leading to term and preterm labor; Project 2 - to achieve a
better understanding of the biology of estrogen signaling through estrogen receptor α (ERα) in the female
reproductive tract during pregnancy and parturition by elucidating the role of ERα acetylation in the function of
the uterus and cervix of pregnant females and the molecular mechanisms by which ERα acetylation controls
ERα-dependent gene regulation in these tissues; Project 3 - to understand the mechanisms by which PRs and
ERs interact to alter gene expression, gestational length, and structural integrity of the cervix during
pregnancy, cervical ripening and parturition, and; Project 4 – to utilize genomic, cell biological and biochemical
approaches to advance our understanding of the mechanisms by which hyaluronan (HA) provides immune-
protection and epithelial barrier function in the pregnant cervix, as well as the molecular mec...

## Key facts

- **NIH application ID:** 9830660
- **Project number:** 5P01HD087150-04
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** WILLIAM Lee KRAUS
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,343,013
- **Award type:** 5
- **Project period:** 2016-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830660

## Citation

> US National Institutes of Health, RePORTER application 9830660, Molecular and Genomic Mechanisms in the Biology of Pregnancy and Parturition (5P01HD087150-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9830660. Licensed CC0.

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