# Regulation of germline function and oocyte quality under stress

> **NIH NIH R15** · MARQUETTE UNIVERSITY · 2020 · $459,000

## Abstract

PROJECT SUMMARY
Fertility in sexual reproducing organisms requires the formation of both sperm and oocyte. One crucial function
of the female germline is the production of high-quality oocytes, which requires both an accurately replicated
genome and full complement of cytoplasmic components. Infertility or progeny with diseases can be caused
by poor quality of oocytes. Understanding how the female germline can respond to environmental stresses to
maintain oocyte quality is important for assessing how infertility occurs in some individuals.
As in the human ovary, the C. elegans hermaphrodite oogenic germline produces many more oogenic germ
cells than mature oocytes. In C. elegans, >50% of oogenic nuclei are lost prior to oocyte formation through
apoptosis. Apoptosis can contribute to oocyte quality through two main mechanisms: removal of low-quality
germ nuclei and addition of cytoplasmic resources to the remaining oocytes. Several environmental stressors,
including moderate temperature stress, lead to an increase in germline apoptosis without inducing DNA
damage. One of the central players necessary for promoting germline apoptosis is LIN-35, the sole C. elegans
homolog of mammalian retinoblastoma. Our preliminary data indicate that the MuvB core of the DREAM
complex, which is known to interact with LIN-35/Rb, also promotes increased germline apoptosis in response
to moderate temperature stress. Our hypothesis is that moderate stress activates apoptosis through LIN-
35/MuvB core to ensure progeny fitness. To investigate this hypothesis, this research project will build on our
expertise in DREAM complex biology and germline temperature response.
We propose three specific aims to investigate the molecular mechanisms of increased apoptosis under
moderate temperature stress and the links between apoptosis and progeny fitness: (1) How does apoptosis in
germlines under moderate temperature stress contribute to changes in nuclear or cytoplasmic quality in the
oogenic germline? (2) How does LIN-35/MuvB promote apoptosis under moderate temperature stress? (3)
Can apoptosis contribute to fertility and fitness in response to moderate temperature stress?
This work will define the signaling pathways that induce increased apoptosis, the direct effects of apoptosis on
germ cell quality and function, and the long-term effects on fertility and population fitness of increased
apoptosis under moderate temperature stress, defining pathways that can be explored to understand infertility.

## Key facts

- **NIH application ID:** 9965184
- **Project number:** 1R15GM137256-01
- **Recipient organization:** MARQUETTE UNIVERSITY
- **Principal Investigator:** Lisa Nicole Petrella
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $459,000
- **Award type:** 1
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965184

## Citation

> US National Institutes of Health, RePORTER application 9965184, Regulation of germline function and oocyte quality under stress (1R15GM137256-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9965184. Licensed CC0.

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