# Mitochondrial dynamics in spermatogonial differentiation

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2024 · $314,078

## Abstract

PROJECT SUMMARY
Mitochondria are increasingly recognized as key players in a wide range of cellular and developmental processes,
such as cell signaling, stem cell self-renewal, and lineage commitment, beyond their canonical roles in
metabolism and oxidative phosphorylation. Such functional diversity is largely determined by the cell type-
specific mitochondrial features, including mitochondrial number, architecture, distribution, and interaction with
other subcellular organelles. These mitochondrial features are tightly regulated via mitochondrial fusion and
fission, collectively known as mitochondrial dynamics, the alteration of which will lead to changing mitochondrial
functions and activities in a cell type-specific manner, and thus impacts cell fate decision, particularly during
development and in stem cell differentiation. We found that upregulated mitochondrial respiration accompanied
by increased reactive oxygen species (ROS) is required for postnatal spermatogonial stem cell differentiation.
However, such elevated ROS can increase mitochondrial DNA mutations that are deleterious to mitochondrial
fitness and cell functions. It remains elusive how stem cells properly balance mitochondrial activities to meet the
competing need for increased mitochondrial respiration during differentiation while maintaining mitochondrial
fitness. Our pilot data suggest that mitochondria fusion and fission are both upregulated in spermatogonial
differentiation, which is essential for sustaining proper male fertility. We thus propose to reveal a novel functional
mechanism of how spermatogonial differentiation and germ cell mitochondrial fitness are regulated by
concurrently accelerated and properly balanced mitochondrial fusion and fission. To achieve this goal, we will
integrate a series of genetically modified mouse models with in vitro spermatogonial differentiation and
transplantation approaches. Study findings will fundamentally advance research in both reproductive medicine
and mitochondrial biology by explaining how spermatogonial differentiation is regulated via stage-specific
mitofusion and fission, thereby unlocking a new area of discovery, namely, how mitochondrial function and health
are maintained so in order to support critical and unique events of mammalian development. In addition, by
revealing the impacts of mitochondrial dynamics on germ cell mitochondrial fitness, this project will critically
inform a novel strategy to treat impaired male fertility due to mitochondrial dysfunctions.

## Key facts

- **NIH application ID:** 10895967
- **Project number:** 5R01GM146587-03
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Yuan Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $314,078
- **Award type:** 5
- **Project period:** 2022-09-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10895967

## Citation

> US National Institutes of Health, RePORTER application 10895967, Mitochondrial dynamics in spermatogonial differentiation (5R01GM146587-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10895967. Licensed CC0.

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