在受精率不同的IVF患者中比较精子蛋白质组学，确定FAM205A是男性不育的新生物标志物
Comparative sperm proteomics in IVF patients with differential fertilization rates identifies FAM205A as a novel biomarker for male infertility.
摘要(中文译文)
本研究确定家族序列相似性205成员A（FAM205A）是一种具有临床意义的顶体蛋白，与男性特发性不育症密切相关。对按受精结局分组的体外受精（IVF）患者精子进行整合蛋白质组学分析（每组n=12；临床验证n=267），结果显示FAM205A表达与受精成功率之间存在强相关性（高表达组为76.3%，低表达组为15.4%，P<0.05），且独立于标准精液参数。利用混合人精子样本（每组n=20）进行的功能分析显示，FAM205A低表达导致钙诱导的顶体反应应答显著降低（28.9% vs 高FAM205A表达组的49.2%，P<0.01），抗FAM205A抗体阻断实验证实了该表型（抑制率为38.1%，P<0.01）。成簇规律间隔短回文重复序列（CRISPR）相关蛋白9（Cas9）基因组编辑系统（CRISPR-Cas9）生成的Fam205a1敲除小鼠（Fam205a1为人FAM205A的小鼠直系同源基因）表现出完全不育，其特征为少精子症、弱精子症、畸形精子症、顶体形成破坏以及精子活力显著降低。Fam205a1敲除小鼠的机制研究揭示，FAM205A缺陷可诱导精子细胞凋亡并损害顶体外排，而后者是精卵融合的关键过程。结果表明，FAM205A通过两种机制调控生育能力：在精子发生过程中维持结构完整性，以及促进顶体反应（AR）。本研究确定FAM205A为特发性男性不育症的可靠诊断生物标志物，并可作为生殖医学中的潜在治疗靶点。
Abstract
This study identified family with sequence similarity 205, member A (FAM205A) as a clinically significant acrosomal protein critically implicated in male idiopathic infertility. Integrated proteomic analysis of sperm from in vitro fertilization (IVF) patients categorized by fertilization outcome ( n = 12 per group; clinical validation, n = 267) revealed a strong correlation between FAM205A expression and fertilization success (76.3% in high-expression groups vs 15.4% in low-expression groups, P < 0.05), independent of standard semen parameters. Functional analyses utilizing pooled human sperm samples ( n = 20 per group) revealed that low FAM205A expression led to a significantly decreased calcium-induced acrosome reaction response (28.9% vs 49.2% in high FAM205A expression, P < 0.01), a phenotype corroborated by anti-FAM205A antibody blockade (38.1% inhibition, P < 0.01). The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) genome editing system (CRISPR-Cas9)-generated knockout mice lacking Fam205a1 , which is the murine ortholog of human FAM205A, exhibited complete infertility, characterized by oligospermia, asthenozoospermia, teratozoospermia, disrupted acrosome formation, and significantly reduced sperm motility. Mechanistic studies in Fam205a1 knockout mice revealed that FAM205A deficiency induces spermatid apoptosis and impairs acrosomal exocytosis, a crucial process for sperm-egg fusion. The results demonstrate that FAM205A regulates fertility through two mechanisms: preserving structural integrity during spermiogenesis and facilitating the acrosomal reaction (AR). This study identified FAM205A as a reliable diagnostic biomarker for idiopathic male infertility and a potential treatment target in reproductive medicine.
如何引用
AMA
Peng Zhang, He-Mei Li, Sai Lu, Li-Qing Fan, Hui Qian, Jiu Yin. Comparative sperm proteomics in IVF patients with differential fertilization rates identifies FAM205A as a novel biomarker for male infertility.. Asian journal of andrology. 2026; doi:10.4103/aja202580.
APA
Peng Zhang, He-Mei Li, Sai Lu, Li-Qing Fan, Hui Qian, Jiu Yin (2026). Comparative sperm proteomics in IVF patients with differential fertilization rates identifies FAM205A as a novel biomarker for male infertility.. Asian journal of andrology. https://doi.org/10.4103/aja202580
GB/T 7714
Peng Zhang, He-Mei Li, Sai Lu, Li-Qing Fan, Hui Qian, Jiu Yin. Comparative sperm proteomics in IVF patients with differential fertilization rates identifies FAM205A as a novel biomarker for male infertility.[J]. Asian journal of andrology, 2026 doi:10.4103/aja202580.
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