Proteomic analysis of human sperm reveals changes in protamine 1 phosphorylation in men with infertility

F&S science Pub Date : 2024-05-01 DOI:10.1016/j.xfss.2023.12.002

Samantha B. Schon M.D. , Lindsay Moritz Ph.D. , Mashiat Rabbani B.S. , Julia Meguid , Brock R. Juliano Ph.D. , Brandon T. Ruotolo Ph.D. , Kenneth Aston Ph.D. , Saher Sue Hammoud Ph.D.

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Abstract

Objective

To perform a comprehensive assessment of protamine (P) isoforms and modifications in human sperm with the aim of identifying how P modifications and isoforms are altered in men with reduced sperm motility and low sperm count.

Design

Cross-sectional.

Setting

Academic medical center.

Patients

A total of 18 men with prior reported pregnancy and normozoospermia (normal sperm), 14 men from couples with infertility and asthenozoospermia (reduced sperm motility), and 24 men from couples with infertility and oligoasthenoteratozoospermia (low sperm count and motility and abnormal sperm morphology).

Intervention(s)

Not applicable.

Main Outcome Measure(s)

Proteomic assessment using both top-down and bottom-up liquid chromatography mass spectrometry (MS) analysis.

Results

A total of 13 posttranslational modifications were identified on P1 and P2 using bottom-up MS, including both phosphorylation and methylation. Top-down MS revealed an unmodified and phosphorylated isoform of P1 and the 3 major isoforms of P2, HP2, HP3, and HP4. Protamine 1 phosphorylation was overall higher in men with male factor infertility compared with those with normal semen analysis (40.5% vs. 32.6). There was no difference in P posttranslational modifications or isoforms of P2 in men with normal vs. abnormal fertility.

Conclusion

Human protamines bear a number of posttranslational modifications, with alterations in P1 phosphorylation noted in the setting of male factor infertility.

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人类精子的蛋白质组分析揭示了不育症男性体内原胺 1 磷酸化的变化

目的对人类精子中的质胺（P）同工酶和修饰进行全面评估，以确定精子活力降低和精子数量少的男性精子中的质胺修饰和同工酶是如何改变的。患者共有 18 名曾报告怀孕且患有正常精子症（正常精子）的男性、14 名不育夫妇中患有无精子症（精子活力降低）的男性以及 24 名不育夫妇中患有少精子症（精子数量少、活力低且精子形态异常）的男性。干预措施：不适用。主要结果测量指标：采用自上而下和自下而上的液相色谱质谱分析进行蛋白质组学评估。结果：采用自下而上的质谱分析在 P1 和 P2 上共发现 13 种翻译后修饰，包括磷酸化和甲基化。自上而下质谱分析发现了 P1 的未修饰和磷酸化同工型以及 P2 的 3 种主要同工型：HP2、HP3 和 HP4。与精液分析正常的男性相比，患有男性因素不育症的男性的原胺1磷酸化率总体较高（40.5% 对 32.6%）。结论人类原胺具有多种翻译后修饰，在男性因素不育的情况下，P1 磷酸化会发生改变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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