Human Zona Pellucida Glycoproteins: Binding Characteristics With Human Spermatozoa and Induction of Acrosome Reaction.

Human Zona Pellucida Glycoproteins: Binding Characteristics With Human Spermatozoa and Induction of Acrosome Reaction.
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DOI:
10.3389/fcell.2021.619868
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发表时间:
2021
影响因子:
5.5
通讯作者:
Gupta SK
Gupta SK
中科院分区:
生物学2区
文献类型:
--
作者:
Gupta SK

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人透明质酸(ZP)基质由四种糖蛋白组成,命名为ZP糖蛋白-1(ZP 1)、-2(ZP 2)、-3(ZP 3)和-4(ZP 4)。编码人类ZP糖蛋白的基因突变是导致女性ZP基质异常和不孕的原因之一。人ZP糖蛋白在“精子-卵母细胞”结合中的相关性已经通过使用表达人ZP蛋白或纯化的天然/重组人ZP蛋白的转基因动物模型来描绘。基于纯化的天然/重组人精子蛋白的研究表明,ZP 1,ZP 3和ZP 4主要结合到获能的顶体完整的人精子,而ZP 2结合到顶体反应的精子。相反,人精子结合到从表达人ZP 2的转基因小鼠系获得的卵子,但不结合到表达人ZP 1、ZP 3和ZP 4的那些,这表明ZP 2在人“精子-卵母细胞”结合中具有重要作用。转基因小鼠的进一步研究表明,人ZP 2的N-末端介导了分类群特异性的人精子-卵母细胞结合。聚糖和蛋白质-蛋白质相互作用都在人类配子相互作用中发挥作用。进一步的研究表明,纯化的天然/重组人ZP 1、ZP 3和ZP 4能够诱导顶体反应。人精子与表达人ZP 1 -4蛋白而非小鼠ZP 1 -3蛋白的转基因小鼠卵子结合,穿透ZP基质并聚集在卵周间隙中,这些精子与顶体反应,表明人ZP 2在转基因小鼠模型中也诱导顶体反应。在人类中,已经显示出N-连接的糖基化的α蛋白在诱导顶体反应中起重要作用。因此,在人类中,基于使用转基因小鼠模型以及纯化的天然/重组α蛋白的研究,可能不止一种α蛋白参与“精子-卵母细胞”结合和顶体反应的诱导。
Human zona pellucida (ZP) matrix is composed of four glycoproteins designated as ZP glycoprotein -1 (ZP1), -2 (ZP2), -3 (ZP3), and -4 (ZP4). Mutations in the genes encoding human ZP glycoproteins are one of the causative factors leading to abnormal ZP matrix and infertility in women. Relevance of the human ZP glycoproteins in ‘sperm–oocyte’ binding has been delineated by using either transgenic animal models expressing human zona proteins or purified native/recombinant human zona proteins. Studies based on the purified native/recombinant human zona proteins revealed that ZP1, ZP3, and ZP4 primarily bind to the capacitated acrosome-intact human spermatozoa whereas ZP2 binds to acrosome-reacted spermatozoa. On the contrary, human spermatozoa binds to the eggs obtained from transgenic mouse lines expressing human ZP2 but not to those expressing human ZP1, ZP3, and ZP4 suggesting that ZP2 has an important role in human ‘sperm–oocyte’ binding. Further studies using transgenic mouse lines showed that the N-terminus of human ZP2 mediate the taxon-specific human sperm–oocyte binding. Both glycans and protein-protein interactions have a role in human gamete interaction. Further studies have revealed that the purified native/recombinant human ZP1, ZP3, and ZP4 are competent to induce acrosome reaction. Human sperm binds to the mouse transgenic eggs expressing human ZP1-4 instead of mouse ZP1-3 proteins, penetrated the ZP matrix and accumulated in the perivitelline space, which were acrosome-reacted suggesting that human ZP2 in transgenic mouse model also induce acrosome reaction. In humans N-linked glycosylation of zona proteins have been shown to play an important role in induction of the acrosome reaction. Hence in humans, based on studies using transgenic mouse model as well as purified native/recombinant zona proteins, it is likely that more than one zona protein is involved in the ‘sperm–oocyte’ binding and induction of the acrosome reaction.
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