PDF(Pubmed)
Abstract：
Defective oocyte maturation is a common cause of female infertility. The loss of the zona pellucida (ZP) represents a specific condition of impaired oocyte maturation. The extracellular matrix known as the ZP envelops mammalian oocytes and preimplantation embryos, exerting significant influence on oogenesis, fertilization, and embryo implantation. However, the genetic factors leading to the loss of the ZP in oocytes are not well understood. This study focused on patients who underwent oocyte retrieval surgery after ovarian stimulation and were found to have abnormal oocyte maturation without the presence of the ZP. Ultrasonography was performed during the surgical procedure to evaluate follicle development. Peripheral blood samples from the patient were subjected to exome sequencing. Here, a novel, previously unreported heterozygous mutation in the ZP1 gene was identified. Within the ZP1 gene, we discovered a novel heterozygous mutation (ZP1 NM_207341.4:c.785A>G (p.Y262C)), specifically located in the trefoil domain. Bioinformatics comparisons further revealed conservation of the ZP1-Y262C mutation across different species. Model predictions of amino acid mutations on protein structure and cell immunofluorescence/western blot experiments collectively confirmed the detrimental effects of the ZP1-Y262C mutation on the function and expression of the ZP1 protein. The ZP1-Y262C mutation represents the novel mutation in the trefoil domain of the ZP1 protein, which is associated with defective oocyte maturation in humans. Our report enhances comprehension regarding the involvement of ZP-associated genes in female infertility and offers enriched understanding for the genetic diagnosis of this condition.
摘要：
卵母细胞成熟缺陷是女性不育的常见原因。透明带(ZP)的丧失代表卵母细胞成熟受损的特定条件。称为ZP的细胞外基质包裹哺乳动物卵母细胞和植入前胚胎，对卵子发生产生重大影响，受精,和胚胎植入。然而,导致卵母细胞中ZP丢失的遗传因素尚不清楚。这项研究的重点是在卵巢刺激后接受卵母细胞取出手术的患者，并且在没有ZP存在的情况下发现卵母细胞成熟异常。在手术过程中进行超声检查以评估卵泡发育。对来自患者的外周血样品进行外显子组测序。这里,一本小说,在ZP1基因中发现了以前未报道的杂合突变。在ZP1基因中，我们发现了一个新的杂合突变（ZP1NM_207341.4：c.785A>G（p。Y262C)),特别位于三叶域。生物信息学比较进一步揭示了不同物种之间ZP1-Y262C突变的保守性。氨基酸突变对蛋白质结构的模型预测和细胞免疫荧光/蛋白质印迹实验共同证实了ZP1-Y262C突变对ZP1蛋白的功能和表达的有害影响。ZP1-Y262C突变代表ZP1蛋白三叶结构域中的新突变，这与人类卵母细胞成熟缺陷有关。我们的报告增强了对ZP相关基因参与女性不育症的理解，并为这种情况的遗传诊断提供了丰富的理解。
