# Control of Meiosis and Germline Proliferation

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $81,936

## Abstract

PROJECT SUMMARY/ABSTRACT
The oocytes of most sexually reproducing animals arrest in diplotene or diakinesis of meiotic prophase I.
Human oocytes enter meiosis in the embryo and maintain prophase arrest for decades. Oocyte growth
occurs during the period of prophase I arrest, which enables them to acquire competence to complete
meiosis and to produce healthy progeny. Hormonal signaling and soma-germline interactions regulate meiotic
resumption (oocyte meiotic maturation). Meiotic maturation is defined by the transition to metaphase I, and its
hallmarks are nuclear envelope breakdown, rearrangement of the cortical cytoskeleton, and meiotic spindle
assembly. A failure of oocytes to undergo meiotic maturation results in sterility, whereas improper execution
of the meiotic divisions causes aneuploidy. The timing of meiotic maturation is crucial. If oocytes undergo
meiotic maturation prematurely, their capacity to produce healthy offspring is diminished. The molecular
mechanisms that control and coordinate oocyte growth and meiotic maturation are incompletely understood.
This application seeks to fill this knowledge gap by studying conserved translational regulators that
coordinate and control the meiotic maturation decision and the growth process. We address mechanistic
questions about how intercellular signaling and translational regulation control meiotic resumption.
 Defects in oogenesis represent a major cause of human birth defects, miscarriage and infertility. Ethical
and technical issues limit the mechanistic depth of human studies. Oocyte meiotic maturation is an ancient
reproductive process and many of its defining features are deeply conserved in evolution. Model systems are
thus indispensable to the analysis of female meiosis. Because the full-grown oocytes of most animals are
transcriptionally quiescent, translational regulation is a major control point. Our understanding of how
signaling controls translation to regulate oocyte growth and meiotic maturation is incomplete. We developed
C. elegans as a genetic model for studying the control of meiotic maturation by hormonal signaling. Our work
shows that C. elegans and mammals share remarkable similarities in the hormonal control of meiotic
maturation. Our Aims are 1) Elucidate how translational regulators control oocyte growth and meiotic
maturation; 2) Define how the SACY-1 DEAD-box RNA helicase regulates oocyte meiotic maturation; and 3)
Determine how soma-germline gap junctions regulate meiotic maturation. The proposed experiments will
provide mechanistic insights into how intercellular signaling and translational regulation control key cellular
events of oocyte meiotic maturation. This basic research in a genetic model system will generate
fundamental knowledge relevant for understanding human reproduction.

## Key facts

- **NIH application ID:** 10019019
- **Project number:** 3R01GM057173-18A1S1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** David Irwin Greenstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $81,936
- **Award type:** 3
- **Project period:** 1998-05-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019019

## Citation

> US National Institutes of Health, RePORTER application 10019019, Control of Meiosis and Germline Proliferation (3R01GM057173-18A1S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10019019. Licensed CC0.

---

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