# Oocyte stage-specific role of ERβ in primordial follicle activation

> **NIH NIH R21** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 · $193,750

## Abstract

SUMMARY
In mammalian ovaries, a fixed number of primordial follicles that are formed during the fetal or early neonatal period
serve as the source of mature oocytes for the entire reproductive lifespan. Uncontrolled or excessive activation of
primordial follicles leads to the depletion of the ovarian reserve, resulting in ovulatory dysfunction. We
demonstrated that estrogen receptor β (ERβ) plays a gatekeeping role during primordial follicle activation (PFA).
In both the rat and the mouse, the absence of ERβ results in increased numbers of primordial follicles being
activated and developing into primary follicles. In a conditional knockout mouse that lacks ERβ in oocytes starting
from the primordial follicle stage, we detected excessive activation of primordial follicles similar to that of Erβnull
mutants. Based on this novel observation, we hypothesize that ERβ regulation of PFA is mediated by its
transcriptional function in the oocytes of primordial or primary follicles. However, it remains unclear if the
regulatory mechanism of ERβ is restricted to the primordial follicles or if it can function in activated primary follicles.
Also, our observations cannot exclude a potential role for ERβ in follicular granulosa cells. In this study, we propose
to define oocyte stage-specific roles of ERβ in the regulation of PFA. Using follicular stage-specific conditional ERβ
knockout mice, we will: 1) determine the role of ERβ in controlling PFA in both primordial and activated oocytes, 2)
assess the ovarian phenotypes following oocyte stage-specific ERβ depletion, 3) perform single cell transcriptome
analyses to identify the ERβ-regulated oocyte genes involved in PFA, and 4) identify any granulosa-specific genes
that are differentially impacted due to oocyte-specific depletion of ERβ. ERβ is a ligand activated nuclear receptor
that has well-characterized selective ligands approved for use in clinical trials. Although it is the predominant
estrogen receptor in the ovary, ERβ has never been targeted to treat ovarian dysfunction. The results of the
proposed research will provide insight into how the molecular targeting of ERβ might enhance our efforts to extend
female reproductive longevity and improve existing assisted reproductive technologies.

## Key facts

- **NIH application ID:** 10493320
- **Project number:** 5R21HD105095-02
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Mohammad A.K. Rumi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $193,750
- **Award type:** 5
- **Project period:** 2021-09-22 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10493320

## Citation

> US National Institutes of Health, RePORTER application 10493320, Oocyte stage-specific role of ERβ in primordial follicle activation (5R21HD105095-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10493320. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*