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Protamine sequence determines species-specific nuclear shape and histone retention.
Marta Czernik1,2, Luca Palazzese1, Dawid Winiarczyk2
1Laboratory of Embryology, Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy.
Iscience
|August 4, 2025
Summary
Protamine 1 (PRM1) cysteine positions critically influence sperm nuclear shape and chromatin condensation. Mutations in mouse PRM1 Cys15 and Cys29 altered sperm head morphology and increased histone retention, impacting male fertility.
Area of Science:
- Reproductive Biology
- Spermatogenesis
- Molecular Biology
Background:
- Protamine 1 (PRM1) is essential for sperm chromatin condensation and nuclear shaping during spermiogenesis.
- The specific roles of PRM1 sequence variations in determining species-specific nuclear morphology are not fully understood.
Purpose of the Study:
- To investigate the functional significance of specific cysteine residues in mouse PRM1 for nuclear shape determination.
- To elucidate the impact of PRM1 cysteine mutations on chromatin condensation and histone retention in spermatozoa.
Main Methods:
- Generation of mutant mice with targeted mutations in PRM1 Cys15 and Cys29.
- Analysis of sperm morphology and count in mutant and wild-type mice.
- Transmission electron microscopy (TEM) to examine chromatin condensation and histone retention.
Main Results:
- Mice with PRM1 Cys15/Cys29 mutations exhibited altered sperm head shapes.
- TEM revealed disrupted chromatin condensation and significantly increased histone retention in mutant sperm.
- No significant changes in sperm count or overall protamine expression levels were observed.
Conclusions:
- Species-specific PRM1 cysteine residue positions are critical for establishing the characteristic nuclear shape of spermatozoa.
- PRM1 cysteines play a key role in regulating histone-to-protamine exchange and ensuring proper chromatin condensation.
- These findings provide insights into the molecular mechanisms underlying sperm nuclear development and male fertility.
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