透明带基因和蛋白与人类生育。

Trends in developmental biology Pub Date : 2020-01-01
Eveline S Litscher, Paul M Wassarman
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摘要

透明带(ZP)是围绕在哺乳动物卵母细胞、卵子和胚胎周围的细胞外基质(ECM),在卵子发生、受精和着床前发育过程中起着至关重要的作用。小鼠和人类的ZP分别由三种或四种称为ZP1-4的独特蛋白质组成,这些蛋白质由卵母细胞在其生长阶段合成、加工和分泌。所有的ZP蛋白都有一个透明带结构域(ZPD),由约270个氨基酸组成,并有8个保守的Cys残基作为4个分子内二硫化物存在。分泌的ZP蛋白在生长的卵母细胞周围聚集成长原纤维,ZP2-ZP3二聚体周期性地沿原纤维排列。原纤维由ZP1交联,形成厚而透明的ECM,精子必须首先与之结合,然后在卵子受精过程中穿透。通过基因靶向使小鼠ZP1、ZP2或ZP3失活会影响卵母细胞周围ZP的形成和生育能力。由于ZP2或ZP3失活导致卵子缺乏ZP的雌性小鼠完全不育,而ZP1失活导致异常ZP的构建和生育能力降低。对不孕女性患者的大量研究结果强烈提示,人类ZP1、ZP2或ZP3基因序列变异(GSV)由点突变、错义突变或移码突变引起,对ZP的形成和女性生育能力具有类似的有害影响。根据我们目前对ZP蛋白合成、加工、分泌和组装的了解,讨论了这些发现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Zona pellucida genes and proteins and human fertility.

The zona pellucida (ZP) is an extracellular matrix (ECM) that surrounds all mammalian oocytes, eggs, and embryos and plays vital roles during oogenesis, fertilization, and preimplantation development. The mouse and human ZP is composed of three or four unique proteins, respectively, called ZP1-4, that are synthesized, processed, and secreted by oocytes during their growth phase. All ZP proteins have a zona pellucida domain (ZPD) that consists of ≈270 amino acids and has 8 conserved Cys residues present as four intramolecular disulfides. Secreted ZP proteins assemble into long fibrils around growing oocytes with ZP2-ZP3 dimers located periodically along the fibrils. The fibrils are cross-linked by ZP1 to form a thick, transparent ECM to which sperm must first bind and then penetrate during fertilization of eggs. Inactivation of mouse ZP1, ZP2, or ZP3 by gene targeting affects both ZP formation around oocytes and fertility. Female mice with eggs that lack a ZP due to inactivation of either ZP2 or ZP3 are completely infertile, whereas inactivation of ZP1 results in construction of an abnormal ZP and reduced fertility. Results of a large number of studies of infertile female patients strongly suggest that gene sequence variations (GSV) in human ZP1, ZP2, or ZP3 due to point, missense, or frameshift mutations have similar deleterious effects on ZP formation and female fertility. These findings are discussed in light of our current knowledge of ZP protein synthesis, processing, secretion, and assembly.

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