# The Role of FOS in the Ovary

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $413,229

## Abstract

Abstract
 Understanding the cellular events underlying ovulation and subsequent corpus luteum (CL) formation is
critically important because these biological processes provide the foundation of our ability to regulate female
fertility. A fundamental cornerstone of the cellular events induced by the preovulatory gonadotropin surge vital
for ovulation and CL formation is the expression of specific transcription factors. However, our knowledge of
the identity and regulatory actions of gonadotropin-induced key transcription factors remains limited.
 A recent study has shed light on a member of the activator protein-1 (AP-1) transcription factor family, FOS
(a.k.a. c-fos), as a key transcription factor involved in follicular development, ovulation, and luteal formation.
Fos-deficient mice failed to ovulate and form CL even when exogenous gonadotropins were administered (1),
indicating that the ovarian expression of Fos is necessary for normal ovulation and luteinization. However, little
to nothing is known exactly how the FOS/AP-1 transcription factor affects these processes in the ovary. Our
preliminary study revealed for the first time that the expression of FOS is highly up-regulated in dominant
follicles collected after hCG administration from normally cycling women and in preovulatory follicles after hCG
administration in mice. Moreover, we demonstrated that FOS regulated the hCG-induced increase in the
expression of key ovulatory genes in human granulosa cells by directly binding to the promoters of these
genes. Based on these novel findings, we hypothesized that FOS/AP-1 plays essential roles in ovulation and
luteal formation/function both in humans and mice.
 Fos null mice displayed a pleiotropic phenotype with significant loss of viability at birth. To determine the
ovary-specific function/action of FOS/AP-1, we propose to establish novel transgenic mouse models in which
Fos expression is ablated in an ovarian cell-specific manner. These mutant mice will be used to assess the
ovarian phenotype including follicular development, ovulation, luteal development, and fertility as well as to
identify downstream target genes of FOS/AP-1 in ovarian cells (Specific Aim #1). To relate and compare the
findings from mice to humans, we will first characterize the spatiotemporally regulated expression of all FOS
and JUN family members in ovulatory follicles obtained before and throughout the periovulatory period from
normally cycling women. The specific role of FOS/AP-1 in human ovaries will also be determined by identifying
downstream target genes of FOS/AP-1 and assessing the cellular impact(s) of FOS' action (Specific Aim #2).
 The information obtained from the proposed studies will not only advance our understanding of the
mechanism necessary for successful ovulation and luteinization but also be instrumental for future
translational/clinical application, thus leading to improved management of fertility in vivo and in vitro.

## Key facts

- **NIH application ID:** 9925796
- **Project number:** 5R01HD096077-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** MISUNG JO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $413,229
- **Award type:** 5
- **Project period:** 2019-05-06 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925796

## Citation

> US National Institutes of Health, RePORTER application 9925796, The Role of FOS in the Ovary (5R01HD096077-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9925796. Licensed CC0.

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