# Signals controlling tissues homeostasis in the ovary

> **NIH VA I01** · OMAHA VA  MEDICAL CENTER · 2020 · —

## Abstract

Recent developments in other fields of research have shed light on an evolutionarily conserved pathway that
controls organ size by regulating cell proliferation, apoptosis, and stem cell self-renewal. This pathway is called
the Hippo signaling pathway and disrupting the Hippo pathway results in the loss of tissue homeostasis and
contributes to many human diseases. Despite extensive study of the Hippo pathway in the past decade, the
exact nature of extracellular signals and membrane receptors regulating the Hippo pathway remains elusive.
Recent studies and our preliminary data demonstrate that YAP and TAZ, the effectors of the Hippo pathway,
play an important role in the ovary. The ovary is a fascinating organ that contributes the maturation of oocytes
and the production of sex hormones, which are important for successful reproduction and quality-of-life. The
ovarian follicle is the functional unit of the ovary. The formation of primordial follicles is a critical cellular transition
process; and the failure of folliculogenesis during fetal life leads to ovarian dysgenesis and premature ovarian
failure. In women the early loss of ovarian function not only causes infertility but also contributes to the onset of
menopause-related complications. The granulosa and theca cells of the follicle proliferate as the follicle develops
and secrete sex hormones and local factors that are critical for successful oocyte maturation. In women and
cattle multiple waves of follicle growth and atresia occur during each reproductive cycle. Follicle development
terminates at ovulation when the granulosa and theca cells differentiate into progesterone secreting luteal cells.
Progesterone is essential for development of the embryo, implantation of the embryo into the uterus and
maintenance of pregnancy. Disruption of folliculogenesis and luteal formation or function results in imbalanced
hormone production, early embryonic failure, and possibly the transformation of cells leading to the development
of tumors. Considering the number of women who suffer from infertility associated with ovarian dysfunction,
understanding mechanisms that regulate the development of follicles, proliferation and differentiation of follicles,
and the function of luteal cells holds great potential to positively impact women's health. There is a gap in our
knowledge of the contributions of the Hippo pathway to follicle development and cellular differentiation of ovarian
granulosa and theca cells which ultimately form the corpus luteum. This proposal will test the hypothesis that
YAP and TAZ are required for follicle development but active Hippo signaling contributes to the differentiation of
granulosa and theca cells. In this proposal we will utilize a tractable in vivo mouse model to study follicle
development and an in vitro cow model to study proliferation and differentiation of follicle cells and luteal function.
Cows are an excellent model for women because cows, like women, are mono-ovulator...

## Key facts

- **NIH application ID:** 9780784
- **Project number:** 1I01BX004272-01A2
- **Recipient organization:** OMAHA VA  MEDICAL CENTER
- **Principal Investigator:** JOHN S DAVIS
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2019-10-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9780784

## Citation

> US National Institutes of Health, RePORTER application 9780784, Signals controlling tissues homeostasis in the ovary (1I01BX004272-01A2). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9780784. Licensed CC0.

---

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