# Control of ovarian vascular remodeling by CCAAT/enhancer binding proteins alpha and beta

> **NIH NIH R01** · CORNELL UNIVERSITY · 2024 · $335,897

## Abstract

PROJECT SUMMARY/ABSTRACT
Infertility occurs in approximately 15% of women of reproductive age in the United States. Approximately half of
the cases involve impaired ovulation, the cause of which is often elusive. The aim of this project is to achieve
new understanding of ovulatory defects that will serve as a foundation for effective treatment of infertility. It is
known that obesity negatively impacts female fertility and ovulation, but the underlying mechanism remains to
be elucidated. Recent findings highlight the crucial role of preovulatory ovarian vascular remodeling in successful
ovulation: the ovulatory luteinizing hormone (LH) surge induces a series of vascular remodeling processes in the
ovary, including changes in vascular permeability, vessel contraction and formation of new blood vessels.
CCAAT/enhancer binding proteins alpha and beta (C/EBPα and C/EBPβ, jointly abbreviated C/EBPα/β) are
rapidly induced in granulosa cells by the LH surge and function as important regulators of ovulation. Based on
our preliminary data, which show the profound effects of C/EBPα/β deficiency on ovarian vascular remodeling in
mice, we hypothesize that C/EBPα and C/EBPβ are key mediators by which the LH surge controls vascular
remodeling in preovulatory ovaries. Given obesity’s negative impact on vascular function in general and on
ovarian blood flow in women in particular, we also propose the novel concept that ovarian vascular remodeling
is a key mediator between obesity and ovulation failure. This proposal first seeks to use murine models of
ovulation failure and disrupted ovarian vascular remodeling to identify their regulatory mechanisms downstream
of the LH surge, then addresses the knowledge deficit around obesity’s impact on ovarian vasculature. To
achieve these goals we will apply 3-dimensional quantitative intravital imaging to a transgenic mouse line with
ovary-specific ablation of C/EBPα/β to first define the specific vascular remodeling events regulated by C/EBPα/β
in preovulatory ovaries, then determine in a diet-induced obese mouse model the impact of obesity on the activity
of C/EBPα/β and vascular remodeling during ovulation. We will further seek understanding of cell type-specific
mechanisms regulating preovulatory vascular remodeling and ovulation using single-cell, next-generation
sequencing technologies; these approaches will also reveal whether epigenetic mechanisms regulating
chromatin accessibility play a key role in preovulatory vascular remodeling and ovulation, and whether C/EBPα/β
mediate this interaction. Successful completion of the proposed studies will advance our understanding of
ovulation regulation and have a major impact by elucidating links among obesity, epigenetic regulation, and
ovarian function, thus enabling improved treatment of many cases of female infertility.

## Key facts

- **NIH application ID:** 10835068
- **Project number:** 5R01HD109392-03
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** YI REN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $335,897
- **Award type:** 5
- **Project period:** 2022-08-16 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10835068

## Citation

> US National Institutes of Health, RePORTER application 10835068, Control of ovarian vascular remodeling by CCAAT/enhancer binding proteins alpha and beta (5R01HD109392-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10835068. Licensed CC0.

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