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Alterations in the abundance of protamine proteoforms related to sperm chromatin packaging, obesity, and age in men with unexplained infertility

ABSTRACT: Protamine1 (P1) and Protamine 2 family (P2) are the most relevant nuclear proteins in the male gamete since are necessary to compact and protect the paternal genome. Human and mouse sperm contain a complex population of protamine proteoforms, which raises the interest to decipher whether it responds to a need of protein redundancy to ensure proper chromatin compaction, or whether specific protamine proteoforms have functional implications. In this study, we apply an optimized strategy based on Top-Down Mass Spectrometry to quantify alterations in the protamine proteoform profile of normozoospermic men with unexplained infertility and either molecular (high P1/P2) or lifestyle (obesity and advanced age) alterations. Accumulation of P2 immature forms was associated to higher P1/P2 ratios, suggesting an impaired processing of P2 in these patients. Men with obesity and intracellular oxidative stress revealed alterations in P1 proteoforms with mass shift(s) of +61 Da, either phosphorylated or not, and advanced age men showed a specific loss of diphosphorylated P1. These results point to alterations on protamine modifying mechanisms, such as proteolysis and phosphorylation, rather than on protamine synthesis, as critical factors for proper sperm chromatin maturity with impact on male fertility

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Semen, Sperm

DISEASE(S): Male Infertility

SUBMITTER: Marta Vilaseca

LAB HEAD: Marta Vilaseca

PROVIDER: PXD049367 | Pride | 2025-04-25

REPOSITORIES: Pride

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			Action	DRS
	3209_AS.fasta	Fasta
	3765_JC_Elderly_7296_P03_I03_R13.raw	Raw
	3765_JC_Elderly_7296_P03_I04_R14.raw	Raw
	3765_JC_Elderly_8552_P04_I04_R16.raw	Raw
	3765_JC_Obesity_7882_P04_I03_R29.raw	Raw

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