# Dynamic Regulation of the Ovarian Reserve

> **NIH NIH R01** · BROWN UNIVERSITY · 2021 · $411,427

## Abstract

Project Summary
Approximately 12% of couples are infertile and 1% of the female population worldwide experiences primary
ovarian insufficiency (POI) which results from a reduction of the ovarian follicle reserve that often leads to
premature menopause and infertility. Important pathological outcomes associated with early menopause include
osteoporosis, cardiovascular and Alzheimer's disease. Although several genes have been linked to women with
POI, about 90% of the cases are idiopathic. By uncovering the developmental and molecular mechanisms
underlying the establishment of the initial pool of primordial follicles and the maintenance of the adult ovarian
reserve in the mouse, we will be poised to better understand, diagnose and treat POI in the future. We have
discovered and characterized the roles of a protein called TAF4b that is essential for establishing the healthy
ovarian follicle reserve in the mouse ovary. TAF4b is a gonadal-enriched subunit of the general transcription
factor TFIID, a large multiprotein complex composed of the TATA-box binding protein (TBP) and 14 TBP-
associated factors (TAFs). Our approach to studying the regulation of ovarian follicle development by TAF4b has
elucidated the ovarian functions of TAF4b in the context of a TAF4b-deficient mouse model. Collectively, these
studies have revealed that TAF4b-deficient female mice suffer from hallmarks of POI including persistent
estrous, elevated serum follicle stimulating hormone (FSH) and accelerated ovarian reserve depletion. In
addition to our own work, a number of additional studies have linked the potential function of human TAF4b in
the regulation of fertility in women. Strikingly, some of the genetic networks regulated by TAF4b in the mouse
ovary appear to be conserved during human fetal ovary development. Together, these data implicate the
potential deregulation of TAF4b-regulated processes in the context of human POI and female infertility. Based
upon our previous studies, we hypothesize that diverse TAF4b-regulated transcriptional events in the developing
mammalian ovary serve to properly maintain normal ovarian aging and fertility. By uncovering the oocyte- and
granulosa cell-specific functions and mechanisms of TAF4b in these studies, we aim to identify novel genes and
expression mechanisms in place to ensure the successful production of high quality oocytes in women and
perhaps one day better diagnose and/or manage patients with POI and other related deficits of human ovarian
health.

## Key facts

- **NIH application ID:** 10165762
- **Project number:** 5R01HD091848-04
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Richard Neil Freiman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $411,427
- **Award type:** 5
- **Project period:** 2018-08-10 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165762

## Citation

> US National Institutes of Health, RePORTER application 10165762, Dynamic Regulation of the Ovarian Reserve (5R01HD091848-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10165762. Licensed CC0.

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