BACKGROUND Sperm head shaping, controlled by the acrosome-acroplaxome-manchette complex, represents a significant morphological change during spermiogenesis and involves numerous proteins expressed in a spatially and temporally specific manner. Defects in sperm head shaping frequently lead to teratozoospermia concomitant with oligozoospermia and asthenozoospermia, but the pathogenic mechanism underlying sperm head shaping, and its role in male infertility, remain poorly understood. OBJECTIVE AND RATIONALE This review aims to summarize the mechanism underlying sperm head shaping, reveal the relationship between gene defects associated with sperm head shaping and male infertility in humans and mice, and explore potential clinical improvements in ICSI treatment. SEARCH METHODS We searched the PubMed database for articles published in English using the keyword ‘sperm head shaping’ in combination with the following terms: ‘acrosome formation’, ‘proacrosomal vesicles (PAVs)’, ‘manchette’, ‘perinuclear theca (PT)’, ‘chromatin condensation’, ‘linker of nucleoskeleton and cytoskeleton (LINC) complex’, ‘histone-to-protamine (HTP) transition’, ‘male infertility’, ‘ICSI’, and ‘artificial oocyte activation (AOA)’. The selected publications until 1 August 2024 were critically summarized, integrated, and thoroughly discussed, and the irrelevant literature were excluded. OUTCOMES A total of 6823 records were retrieved. After careful screening, integrating relevant literature, and excluding articles unrelated to the topic of this review, 240 articles were ultimately included in the analysis. Firstly, we reviewed the important molecular events and structures integral to sperm head shaping, including PAV formation to fusion, acrosome attachment to the nucleus, structure and function of the manchette, PT, chromatin condensation, and HTP transition. Then, we set forth human male infertility associated with sperm head shaping and identified genes related to sperm head shaping resulting in teratozoospermia concomitant with oligozoospermia and asthenozoospermia. Finally, we summarized the outcomes of ICSI in cases of male infertility resulting from mutations in the genes associated with sperm head shaping, as well as the ICSI outcomes through AOA for infertile men with impaired sperm head. WIDER IMPLICATIONS Understanding the molecular mechanisms of sperm head shaping and its relationship with human male infertility holds profound clinical implications, which may contribute to risk prediction, genetic diagnosis, and the potential treatment of human male infertility.

中文翻译：

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精子头部塑造及其在人类男性生育能力中的作用的分子见解

背景 受顶体-冠状体-manchette 复合物控制的精子头部塑造代表了精子发生过程中的显着形态变化，并涉及以空间和时间特异性方式表达的许多蛋白质。精子头部塑造的缺陷经常导致畸胎精子症，伴有少精子症和弱精子症，但精子头部塑造的致病机制及其在男性不育症中的作用仍然知之甚少。目的和基本原理本文旨在总结精子头部塑造的潜在机制，揭示与精子头部塑造相关的基因缺陷与人类和小鼠雄性不育之间的关系，并探讨 ICSI 治疗的潜在临床改善。检索方法 我们在 PubMed 数据库中检索了使用关键字 “sperm head shaping” 和以下术语以英文发表的文章： “顶体形成”、“顶体前囊泡 （PAV）”、“manchette”、“核周膜腔 （PT）”、“染色质浓缩”、“核骨架和细胞骨架的连接子 （LINC） 复合物”、“组蛋白到鱼精蛋白 （HTP） 转变”、“男性不育”、“ICSI”和“人工卵母细胞活化 （AOA）”。对截至 2024 年 8 月 1 日的入选出版物进行了批判性总结、整合和深入讨论，并排除了不相关的文献。结果 共检索到 6823 条记录。经过仔细筛选，整合相关文献，排除与本综述主题无关的文章，最终纳入 240 篇文章。 首先，我们回顾了精子头部塑造不可或缺的重要分子事件和结构，包括 PAV 形成到融合、顶体附着在细胞核上、下颌的结构和功能、PT、染色质浓缩和 HTP 转换。然后，我们提出了与精子头部塑造相关的人类男性不育症，并确定了与精子头部塑造相关的基因，导致畸胎精子症伴随着少精子症和弱精子症。最后，我们总结了 ICSI 在与精子头塑造相关的基因突变导致男性不育病例中的结果，以及通过 AOA 对精子头受损的不育男性的 ICSI 结果。更广泛的影响 了解精子头部塑造的分子机制及其与人类男性不育症的关系具有深远的临床意义，这可能有助于风险预测、遗传诊断和人类男性不育症的潜在治疗。