# Grem1 and Grem2 in embryonic ovary development

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $316,800

## Abstract

PROJECT SUMMARY
 Normally, women undergo menopause in their early fifties due to exhaustion of the pool of oocytes called
the “ovarian reserve”. Oocytes are generated in large numbers during embryonic development, but the vast
majority undergo programmed cell death; the remaining oocytes become enclosed within quiescent primordial
follicles that make up the ovarian reserve. Pathologic development of the ovarian reserve leads to infertility or
early reproductive senescence. Furthermore, meiotic errors in oocytes cause germ cell death or result in
developmental defects such as aneuploidy. The molecular signals within the embryonic ovary that determine the
upper and lower limits for oocyte numbers are unknown. The long-term goal of our laboratory is to identify
signaling pathways that control oogenesis and thus, female reproductive lifespan. The bone morphogenetic
proteins (BMPs) are a large subgroup of the transforming growth factor beta family and have conserved roles in
primordial germ cell specification and development. The BMPs are known morphogens whose activity must be
strictly regulated during development or pathology and disease results. There are a number of secreted
extracellular BMP-binding proteins that act as molecular sinks to negatively regulate the amount of BMP “sensed”
by a signal-receiving cell. Two of these BMP antagonists, GREMLIN-1 and GREMLIN-2 have genetic variants
associated with primary ovarian insufficiency (POI) in women. We tested the developmental role of Grem1 and
Grem2 by generating single and double knockout mice for Grem1 and Grem2. These mice display a range of
defects in embryonic ovary development including changes to oocyte number and altered meiosis. The aims of
this proposal are designed to (1) determine how loss of Grem1 and/or Grem2 alters embryonic ovary
development; and (2) determine which signaling pathways are dysregulated in embryonic ovaries of mutant mice
that drive changes in germ cell numbers. Collectively, our studies stand to uncover fundamental mechanism that
regulate embryonic ovary development and oocyte numbers, which are essential for mammalian female
reproduction and reproductive lifespan.

## Key facts

- **NIH application ID:** 10830913
- **Project number:** 5R01HD108153-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** STEPHANIE A. PANGAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $316,800
- **Award type:** 5
- **Project period:** 2023-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10830913

## Citation

> US National Institutes of Health, RePORTER application 10830913, Grem1 and Grem2 in embryonic ovary development (5R01HD108153-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10830913. Licensed CC0.

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