# Modeling ovarian aging phenotype in mechanically tuned 3D matrices

> **NIH NIH F30** · NORTHWESTERN UNIVERSITY · 2020 · $40,664

## Abstract

PROJECT SUMMARY
Ovarian aging is associated with fibrosis, a changing female hormone profile, and a decline in oocyte quality
and quantity, resulting in sequelae such as cardiovascular disease, osteoporosis, and infertility. Even before
menopause, there are significant age-related changes in hormone production and oocyte quality. Ovarian
aging is a fibrotic process involving dramatic extracellular matrix remodeling, resulting in an increasingly rigid
microenvironment. While it is known that ECM-derived signals regulate steroidogenesis, the causative
relationship between matrix mechanics and function has not previously been demonstrated. Thus, in the
studies proposed herein, I will test the hypothesis that mechanical changes in the follicle microenvironment
cause a progressive decline in hormone production and egg quality in an aging mouse model. In preliminary
studies, we have demonstrated that 3D-printed gelatin scaffolds – which can be experimentally tuned to
different rigidities— support ovarian follicle survival, growth, and function. In Aim 1, I will experimentally
manipulate the stiffness of the 3D printed gelatin scaffolds in order to define the effects of rigidity on follicle
structure and function and oocyte quality. Specifically, I hypothesize that I can phenocopy older follicles (i.e.
diminished hormone production and oocyte quality) by culturing follicles isolated from younger mice in more
rigid scaffolds. Conversely, I will perform a rescue experiment with follicles from older animals cultured in a
softer scaffold. In Aim 2, proposed experiments will test a possible mechanism of follicle
mechanotransduction. In many cell types, Rho/ROCK signaling is responsible for converting mechanical cues
into biological response. Moreover, in preliminary studies, we demonstrate that Rho, phospho-Rho, and ROCK
are present in discrete follicles in the murine ovary, indicating that Rho signaling is an available molecular
mechanism for follicle mechanotransduction. I will assay Rho/ROCK signaling in reproductively younger and
older mouse cohorts. Additionally, I will test Rho/ROCK signaling in follicles cultured in 3D printed scaffolds of
various rigidities and in the presence of pathway inhibitors. These studies will test my overarching hypothesis
that the mechanical properties of the ovarian matrix play a role in age-related ovarian dysfunction (decline in
hormone production and egg quality), possibly via mechanosensitive Rho/ROCK signaling. Moreover, these
mechanically-tunable 3D-printed scaffolds represent novel in vitro models of ovarian aging and provide a
platform for drug discovery and development that may revolutionize the treatment of age-related female
infertility.

## Key facts

- **NIH application ID:** 9973042
- **Project number:** 5F30AG058387-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Emma Gargus
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,664
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973042

## Citation

> US National Institutes of Health, RePORTER application 9973042, Modeling ovarian aging phenotype in mechanically tuned 3D matrices (5F30AG058387-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9973042. Licensed CC0.

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