# Ovarian reserve formation and maintenance

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $200,208

## Abstract

ABSTRACT
The goal of this study is to understand how epigenetic states in oocytes that reside in primordial follicles
contribute to maintenance of the ovarian reserve in women. The ovarian reserve defines female reproductive
lifespan, which in humans spans decades due to maintenance of meiotic arrest in oocytes residing in
primordial follicles. The quality and quantity of oocytes are critical determinants for ovarian functions, and
exhaustion of primordial follicles triggers menopause. However, our understanding how the ovarian reserve is
generated and maintained is currently limited due to the inability to perform molecular analysis. In our
unpublished study, we developed a protocol to isolate the pool of non-growing oocytes that enabled molecular
analyses. We found that the Polycomb Repressive Complex 1 establishes repressive chromatin states in
perinatal mouse oocytes that directly suppress the gene expression program of meiotic prophase-I and thereby
enable the transition to dictyate arrest. Based on these findings, we propose that the chromatin state is
established during perinatal oogenesis that enables ovarian reserve formation and then maintained in adult
and aged ovaries. In Aim 1, we will perform a comprehensive chromatin profiling of the initial pools of non-
growing oocytes from juvenile ovaries and the ovarian reserve maintained in adulthood. Aim 1 will establish an
epigenome data resource of the ovarian reserve. In Aim2, we designed a candidate-based approach to define
the regulatory mechanism of chromatin states in the ovarian reserve. We will determine the function of CHD4,
a chromatin remodeler, in maintaining the ovarian reserve. Aim 2 will provide the foundation to investigate the
chromatin-based maintenance mechanisms of the ovarian reserve. The proposed research will significantly
advance the field by providing molecular insights how the epigenome of the ovarian reserve is established and
maintained.

## Key facts

- **NIH application ID:** 10772155
- **Project number:** 5R21HD110146-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Satoshi Namekawa
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $200,208
- **Award type:** 5
- **Project period:** 2023-02-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10772155

## Citation

> US National Institutes of Health, RePORTER application 10772155, Ovarian reserve formation and maintenance (5R21HD110146-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10772155. Licensed CC0.

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