SPERM FACTORS AND EGG ACTIVATION: ICSI and the discovery of the sperm factor and PLCZ1.
SPERM FACTORS AND EGG ACTIVATION: ICSI and the discovery of the sperm factor and PLCZ1.
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DOI：
10.1530/rep-21-0487
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发表时间：
2022-05-23
期刊：
影响因子：
3.8
通讯作者：
Fissore, Rafael A.
中科院分区：
文献类型：
--
作者：
Gupta, Neha;Akizawa, Hiroki;Lee, Hoi Chang;Fissore, Rafael A.
近20年前，PLC β 1作为哺乳动物精子中主要的Ca 2+振荡诱导因子的发现，代表了我们寻求阐明受精过程中促进卵子激活的分子和途径的重大突破。胞浆内单精子注射技术的出现，使受精成为可能，而无需精子获能，顶体反应和配子融合，加强了导致发现PLC E1的研究，并成为人类重要的临床工具。使用ICSI结合检测不孕症患者中的PLC E1表达和突变，确立了PLC E1在人类生育中的基本作用，同时发现了核周膜的新成分，这是PLC E1在受精前在精子中的居住部位。值得注意的是，在人类和小鼠以外的物种中更广泛地使用ICSI显示出不佳的成功，并暴露了我们对PLC β 1释放和/或激活的理解的差距。同样，使用缺乏Plc β 1的小鼠模型的精子进行受精也产生了惊人的结果，其真正的含义尚未确定。尽管如此，这些未解决的问题的答案将产生一个完整的图片的适应和分子的球员，哺乳动物物种采用，以确保成功的胚胎发育的触发事件，已经连接世代以来的开始。
The discovery of PLCζ1 nearly twenty years ago as the primary Ca2+ oscillation inducing factor in the sperm of mammals represented a significant breakthrough in our quest to elucidate the molecules and pathways that promote egg activation during fertilization. The advent of the Intracytoplasmic Sperm Injection technique, which made fertilization possible without sperm capacitation, acrosome reaction, and gamete fusion, strengthened the research that led to the discovery of PLCζ1 and became an essential clinical tool for humans. The use of ICSI combined with the detection of PLCζ1 expression and mutations in infertile patients established the fundamental role of PLCζ1 in human fertility while leading to the discovery of novel components of the perinuclear theca, the site of the residence of PLCζ1 in sperm before fertilization. Remarkably, the more extensive use of ICSI in species other than humans and mice revealed poor success and exposed gaps in our understanding of PLCζ1 release and/or activation. Similarly, fertilization using sperm from mouse models lacking Plcζ1 has produced striking results whose true implications are yet to be determined. Nevertheless, answers to these unresolved questions will produce a complete picture of the adaptations and molecular players that mammalian species employ to ensure the success of the triggering event of embryo development that has linked generations since the beginning of times.