Proteomic Analysis of Dpy19l2-Deficient Human Globozoospermia Reveals Multiple Molecular Defects

Dpy19l2 缺陷型人类球形精子症的蛋白质组学分析揭示了多种分子缺陷

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作者:Yueshuai Guo, Jiayin Jiang, Haotian Zhang, Yang Wen, Hao Zhang, Yiqiang Cui, Jianyu Tian, Min Jiang, Xiaofei Liu, Gaigai Wang, Yan Li, Zhibin Hu, Zuomin Zhou, Jiahao Sha, Daozhen Chen, Xiaoyu Yang, Xuejiang Guo

Conclusions and clinical relevance

The present study is the first to analyze total globozoospermia with Dpy19l2 deletion using high-throughput proteomics. This study may provide insights into the mechanism of globozoospermia.

Purpose

To investigate the differences in protein expression between Dpy19l2-deficient human globozoospermia and normozoospermia. Experimental design: Human sperm samples from three globozoospermic donors with Dpy19l2 deletion and three normal controls are subjected to TMT quantitative technology. SPESP1, HIST1H4A, and LYZL1 are randomly selected for western blotting analysis. GO annotations are performed using the Database for Annotation, Visualization, and Integrated Discovery.

Results

A total of 2567 proteins are identified, of which 2510 proteins are quantified, and 491 are differentially expressed (fold-change > 2), with 370 upregulated and 121 downregulated in globozoospermic patients. The levels of several important proteins, including SPACA 1, IZUMO1, ZPBP1, and PLCZ1, are decreased in globozoospermic sperm. Bioinformatics analysis indicates the Dpy19l2-deficient sperm presented molecular defects in acrosome, chromatin, sperm-egg interaction, and fertilization. Conclusions and clinical relevance: The present study is the first to analyze total globozoospermia with Dpy19l2 deletion using high-throughput proteomics. This study may provide insights into the mechanism of globozoospermia.

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