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父本工具包与胚胎发育和健康。

The paternal toolbox for embryo development and health.

机构信息

9.baby Family and Fertility Center, Bologna, Italy.

出版信息

Mol Hum Reprod. 2021 Jul 1;27(7). doi: 10.1093/molehr/gaab042.

Abstract

The sperm is essential for reconstitution of embryonic diploidy and highly specialized developmental functions. Immediately after gamete fusion, the sperm-borne PLC-zeta triggers activation, generating intracellular free Ca2+ oscillations. Mutations in the PLC-zeta encoding gene are associated with the absence of this factor in mature sperm and inability to achieve fertilization. Sperm play also a role in the greater game of the choreography of fertilization. In the human, the sperm centrioles are introduced into the oocyte environment with gamete fusion. They interact with the oocyte cytoskeletal apparatus to form a functional pair of centrosomes and ultimately regulate pronuclear juxtaposition in preparation for the first cleavage. As a consequence, the fidelity of chromosome segregation during the first cell divisions depends on the function of sperm centrioles. Sperm DNA integrity is essential for embryo development and health. Damaged DNA does not impact on the sperm fertilization ability following ICSI. However, detrimental effects emerge at pre- and post-implantation stages. Sperm-specific epigenetic factors also play an active role in the regulation of embryonic development, as shown by correlations between reduced embryo morphological quality and incorrect chromatin packaging during spermiogenesis or abnormal methylation of sperm CpG islands. This functional landscape demonstrates that the contribution of the sperm to development goes far beyond its well-established role in fertilization. Clinical studies confirm this view and indicate sperm function as a crucial aspect of research to increase the efficacy of assisted reproduction treatments.

摘要

精子对于胚胎二倍体的重建和高度特化的发育功能至关重要。在配子融合后,精子携带的 PLC-zeta 立即触发激活,产生细胞内游离 Ca2+ 振荡。编码 PLC-zeta 的基因突变与成熟精子中缺乏这种因子以及无法实现受精有关。精子在受精这一大戏中也扮演着重要角色。在人类中,精子中心粒在配子融合时被引入卵母细胞环境中。它们与卵母细胞细胞骨架相互作用,形成一对功能中心体,并最终调节核仁并列,为第一次分裂做准备。因此,第一次细胞分裂过程中染色体分离的准确性取决于精子中心粒的功能。精子 DNA 完整性对于胚胎发育和健康至关重要。受损的 DNA 不会影响 ICSI 后的精子受精能力。然而,在植入前和植入后阶段会出现不利影响。精子特异性表观遗传因素也在胚胎发育的调控中发挥着积极作用,这可以通过精子发生过程中胚胎形态质量降低和染色质包装不正确或精子 CpG 岛甲基化异常之间的相关性来证明。这种功能景观表明,精子对发育的贡献远远超出了其在受精中确立的作用。临床研究证实了这一观点,并指出精子功能是提高辅助生殖治疗效果的研究的一个关键方面。

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