Purpose

Oocyte activation is a fundamental event at mammalian fertilization. In mammals, this process is initiated by a series of characteristic calcium (Ca²⁺) oscillations, induced by a sperm-specific phospholipase C (PLC) termed PLCzeta (PLCζ). Dysfunction/reduction/deletion of PLCζ is associated with forms of male infertility where the sperm is unable to initiate Ca²⁺ oscillations and oocyte activation, specifically in cases of fertilization failure. This review article aims to systematically summarize recent advancements and controversies in the field to update expanding clinical associations between PLCζ and various male factor conditions. This article also discusses how such associations may potentially underlie defective embryogenesis and recurrent implantation failure following fertility treatments, alongside potential diagnostic and therapeutic PLCζ approaches, aiming to direct future research efforts to utilize such knowledge clinically.

Methods

An extensive literature search was performed using literature databases (PubMed/MEDLINE/Web of Knowledge) focusing on phospholipase C zeta (PLCzeta; PLCζ), oocyte activation, and calcium oscillations, as well as specific male factor conditions.

Results and discussion

Defective PLCζ or PLCζ-induced Ca²⁺ release can be linked to multiple forms of male infertility including abnormal sperm parameters and morphology, sperm DNA fragmentation and oxidation, and abnormal embryogenesis/pregnancies. Such sperm exhibit absent/reduced levels, and abnormal localization patterns of PLCζ within the sperm head.

Conclusions

Defective PLCζ and abnormal patterns of Ca²⁺ release are increasingly suspected a significant causative factor underlying abnormalities or insufficiencies in Ca²⁺ oscillation-driven early embryogenic events. Such cases could potentially strongly benefit from relevant therapeutic and diagnostic applications of PLCζ, or even alternative mechanisms, following further focused research efforts.

中文翻译：

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磷脂酶 C zeta 缺陷与男性不育症之间的关联性日益增强：不仅仅是 ICSI 失败？

目的

卵母细胞激活是哺乳动物受精的基本事件。在哺乳动物中，这一过程是由一系列特征性钙 (Ca ²⁺ ) 振荡启动，这些振荡是由称为 PLCzeta (PLCζ) 的精子特异性磷脂酶 C (PLC) 诱导的。PLC 的功能障碍/减少/缺失与男性不育症有关，其中精子无法启动 Ca ²⁺振荡和卵母细胞激活，特别是在受精失败的情况下。本文旨在系统地总结该领域的最新进展和争议，以更新 PLC 与各种男性因素条件之间不断扩大的临床关联。本文还讨论了这种关联如何可能成为胚胎发生缺陷和生育治疗后反复植入失败的潜在原因，以及潜在的诊断和治疗性 PLCze 方法，旨在指导未来的研究工作在临床上利用这些知识。

方法

使用文献数据库（PubMed/MEDLINE/Web of Knowledge）进行了广泛的文献检索，重点关注磷脂酶 C zeta（PLCzeta；PLCζ）、卵母细胞活化和钙振荡以及特定的男性因素条件。

结果与讨论

有缺陷的 PLC 或 PLC 诱导的 Ca ²⁺释放可能与多种形式的男性不育症有关，包括异常的精子参数和形态、精子 DNA 碎片和氧化以及异常的胚胎发生/妊娠。此类精子在精子头部内表现出 PLCz 水平缺失/降低以及异常定位模式。

结论

有缺陷的 PLC 和 Ca ²⁺释放的异常模式越来越多地被怀疑是 Ca ²⁺振荡驱动的早期胚胎发生事件异常或不足的重要致病因素。随着进一步集中研究工作，此类病例可能会从 PLC z 的相关治疗和诊断应用甚至替代机制中受益匪浅。