ZP1基因突变在空卵泡综合征中的研究进展

doi:10.12280/gjszjk.20230443

摘要/Abstract

摘要：

空卵泡综合征（empty follicle syndrome）发病机制尚不清楚，越来越多的研究聚焦于遗传因素，尤其是调控卵母细胞发育的相关基因。其中，透明带糖蛋白1（zona pellucida glycoprotein 1，ZP1）是透明带基质结构完整性的关键组成部分。由ZP1基因突变造成的透明带结构和功能的缺陷常会导致卵母细胞成熟障碍、脆性增加，进而造成反复取卵失败。现已鉴定出多种导致空卵泡综合征表型的ZP1基因突变。综述不同部位ZP1基因突变引起空卵泡综合征表型及其作用机制。

关键词: 卵泡, 透明带糖蛋白类, 透明带, 基因, 突变, 卵母细胞抽取, 空卵泡综合征

Abstract:

The pathogenesis of empty follicle syndrome has not been clarified. More and more research has focused on the genetic factors of empty follicle syndrome, especially the genes involved in regulating oocyte development. Zona pellucida glycoprotein 1 (ZP1) is a key component of the structural integrity of the zona pellucida matrix. Structural and functional defects of zona pellucida due to the mutations of ZP1 gene often lead to the impaired oocyte maturation and the increased fragility, which may lead to the repeated oocyte retrieval failures. Various mutations of ZP1 gene that cause empty follicle syndrome phenotypes have been identified. In this paper, we reviewed the action and mechanism of ZP1 gene mutations at different sites in causing the empty follicle syndrome phenotype.

Key words: Ovarian follicle, Zona pellucida glycoproteins, Zona pellucida, Genes, Mutation, Oocyte retrieval, Empty follicle syndrome

曹媛媛, 贾赞慧, 张春苗. ZP1基因突变在空卵泡综合征中的研究进展[J]. 国际生殖健康/计划生育杂志, 2024, 43(2): 127-131.

CAO Yuan-yuan, JIA Zan-hui, ZHANG Chun-miao. Research Progress of ZP1 Gene Mutation in Empty Follicle Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2024, 43(2): 127-131.

图/表 3

图1 ZP1~ZP4蛋白的结构图注：本图仅对ZP1蛋白进行了氨基酸数的标注。ZP1和ZP4具有一个与ZPD相邻的TD，在多肽的N端和TD之间有一个额外的ZP-N亚结构域（N1）。ZP2在多肽的N端和ZPD之间有3个额外的ZP-N的亚结构域（N1~N3）。

图2 导致空卵泡综合征的ZP1基因及ZP1蛋白突变位点汇总注：人ZP1基因有12个外显子并编码638个氨基酸。灰色模块1~12代表外显子，蓝色模块为ZP1蛋白结构域。

图3 新生ZP蛋白组装的一般机制注：在所有的ZPD前体蛋白中，ZPD由ZP-N和ZP-C两个亚结构域组成，其后是CTP；CTP含有一个基本的切割位点，如前体蛋白转换酶（Furin）切割位点（CFCS，品红色），以及一个EHP（紫色）和一个TMD（黄色）锚定位点。A 前体在细胞内不聚合，这是由于EHP和IHP（灰色）之间的直接相互作用，因为它们采用依赖于两个疏水片断存在的构象。B Furin（在CFCS处裂解，以十字为标志）在CFCS的C端加工导致成熟蛋白从EHP中解离。C 激活ZPD，暴露聚合元件ZP-N。D 聚合组装成纤维和基质。

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