Protamine sequence determines species-specific nuclear shape and histone retention

The nuclear shape observed after the forced expression of mouse or human protamine 1 (PRM1) in fibroblasts led us to propose the hypothesis that the PRM1 sequence plays an important role in imposing the overall shape of the protaminized nucleus. Comparison of mouse and human PRM1 sequences pointed to cysteines 15 and 29 as potential critical residues in the mouse PRM1 sequence, inducing the characteristic mouse “hooked” nuclear sperm shape. To explore this idea, mice with mutations in PRM1 Cys15 and Cys29 were generated. These mice remained fertile with no significant changes in sperm count or protamine expression levels. However, modifications in sperm head shape were observed. Transmission electron microscopy revealed disrupted chromatin condensation in mutant sperm, with several morphological changes and a remarkable increase in histone retention. Overall, the findings suggest that species-specific PRM1 cysteine residue positions are crucial for nuclear shape determination and histone retention in spermatozoa.