# Homeostatic to reactive hyaluronan matrices in ovarian reproductive aging

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $324,506

## Abstract

PROJECT SUMMARY
Aging is universal and underlies chronic disease as well as tissue and cellular deterioration. The female
reproductive system is the first to age in humans, with functional loss occurring decades prior to other organs.
Reproductive aging is associated with both a decline in the number of eggs within the ovary and a decrease in
their quality, which together, contribute to increased incidences of miscarriages, infertility, and birth defects.
Our long-term objective is to attenuate the negative consequences of female reproductive aging, which are
becoming more prevalent as women globally are delaying childbearing. Reproductive transitions, such as
reproductive aging, is a priority of the Fertility and Infertility branch of the National Institutes of Health, and thus
our work is tightly aligned with the mission of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development. Although considerable research has focused on age-associated changes in the egg,
correspondingly less is known about how the ovarian stroma, the microenvironment in which the egg develops,
changes with age and influences egg quality. A key stromal molecule found in the ovaries is hyaluronan.
Hyaluronan is synthesized and fragmented in inflamed tissues and provides signals that exacerbate
inflammation and drive fibrosis in several organs. Changes in hyaluronan are also implicated in aging tissues.
Here, we will test the overarching hypothesis that ovarian hyaluronan levels decrease with age along with a
corresponding increase in fragmentation of existing HA into a population of small molecules central to the
pathogenesis of ovarian fibrosis and inflammation, which impacts egg quality. This hypothesis will be tested in
three specific aims. First, we will examine how hyaluronan content, fragmentation, and function change in the
ovary with advanced reproductive age. These studies will be performed using reproductively young and
reproductively old mice and will include analysis of ovarian biomechanical properties and the impact of
hyaluronan fragmentation on ovarian follicle development. Second, we will investigate the extent to which
perturbation of hyaluronan expression in vivo induces ovarian stromal inflammation and fibrosis. To
accomplish this goal, we will evaluate indices of inflammation and fibrosis in mice genetically or
pharmacologically deficient in hyaluronan and correlate this with fertility. Third, we will determine how human
ovarian and follicular fluid hyaluronan levels and fragmentation profiles change with age using human material
provided by two established research repositories at Northwestern University. We will investigate the clinical
relevance of our findings by correlating hyaluronan levels and fragmentation profiles with reproductive aging
markers and pregnancy outcomes after assisted reproductive technologies. The premise that the ovarian
stroma contributes to reproductive aging represents a novel research frontier. Com...

## Key facts

- **NIH application ID:** 9858375
- **Project number:** 5R01HD093726-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Francesca E. Duncan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $324,506
- **Award type:** 5
- **Project period:** 2018-02-06 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858375

## Citation

> US National Institutes of Health, RePORTER application 9858375, Homeostatic to reactive hyaluronan matrices in ovarian reproductive aging (5R01HD093726-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9858375. Licensed CC0.

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