Tuesday, November 18, 2025 11/18/2025

Mitochondrial dynamics in spermatogonial differentiation

Award Number: R01GM146587
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Mitochondrial dynamics in spermatogonial differentiation - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $313,808 )
2025	2025	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	4	7/18/2025	NON-COMPETING CONTINUATION	$313,808
														Subtotal = $313,808

Issue Date FY: 2024 ( Subtotal = $314,078 )
2024	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	3	7/31/2024	NON-COMPETING CONTINUATION	$314,078
														Subtotal = $314,078

Issue Date FY: 2023 ( Subtotal = $529,289 )
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	002	2	9/6/2023	SUPPLEMENT FOR EXPANSION	$156,500
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	1	6/12/2023	SUPPLEMENT FOR EXPANSION	$58,451
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	001	2	7/28/2023	NON-COMPETING CONTINUATION	$314,338
														Subtotal = $529,289

Issue Date FY: 2022 ( Subtotal = $314,587 )
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	1	8/18/2022	NEW	$314,587
														Subtotal = $314,587

Grand Total All Awards = $1,471,762

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Mitochondrial dynamics in spermatogonial differentiation

Award Number: R01GM146587

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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