# Understanding the role of meiotic misregulation in germ cell tumor formation

> **NIH NIH P20** · DARTMOUTH COLLEGE · 2024 · $262,400

## Abstract

Meiosis is precisely regulated to ensure the transmission of half the genome into gametes. During meiosis, germ cells 
undergo one round of DNA replication followed by two rounds of chromosome segregation. In mammalian females, 
meiosis is an error-prone process, resulting in a high fraction of eggs with missing or extra chromosomes or that are 
not competent for fertilization. These errors can cause severe consequences including miscarriage, trisomy conditions, 
infertility, germ cell tumor formation, and ovarian germ cell cancer. Therefore, determining the molecular 
mechanisms underlying meiotic regulation is critically important for understanding the etiology of these disorders. 
The objective of this proposal is to investigate how meiosis II is controlled to ensure an egg competent for fertilization 
and to understand how errors in meiosis II regulation result in uncontrolled cell proliferation and the formation of 
germ cell tumors. These studies employ the use of mouse as a mammalian model system to use the tools available to 
address mechanistic questions. Female mice are used to study the oogenesis-specific question of how eggs arrest in 
meiosis II to await fertilization from sperm before completing the second meiotic division. The rationale for the 
proposed research is that the questions were chosen to focus on the understudied and poorly understood process of 
meiosis II regulation, which is important to ensure competent eggs and to prevent germ cell tumor formation. These 
findings are likely to be highly conserved in mammals, such that the results from mouse oogenesis will uncover 
general mechanisms of meiotic regulation during human oogenesis. The experiments are guided by the following 
specific aims proposed: 1) Determine how CDK-cyclin B1 activity is regulated for meiosis II and meiosis II arrest; 
and, 2) Investigate how mos-/- mutant eggs undergo inappropriate cell divisions and identify other meiotic regulators 
whose loss could cause ovarian germ cell tumors. For Aim 1, novel hypotheses are tested that address how protein 
translation and degradation are regulated during meiosis II and how RNA-binding proteins release mRNAs with 
appropriate timings. In Aim 2, the results will reveal how meiosis is mis-regulated when the MOS/MAPK signaling 
pathway is disrupted. Finally, new meiosis II regulators will be discovered. The innovative approaches of combining 
the latest imaging and genomics technologies with the power of in vitro oocyte maturation will allow the discovery of 
new mechanisms of meiotic regulation. The proposed research is significant because the results will reveal general 
principles of meiotic regulation and will identify new targets for germ cell cancer prevention.

## Key facts

- **NIH application ID:** 10904766
- **Project number:** 5P20GM113132-09
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Soni Lacefield
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $262,400
- **Award type:** 5
- **Project period:** 2016-05-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904766

## Citation

> US National Institutes of Health, RePORTER application 10904766, Understanding the role of meiotic misregulation in germ cell tumor formation (5P20GM113132-09). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10904766. Licensed CC0.

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