Center of Reproductive Medicine, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Hum Mutat. 2019 Nov;40(11):2001-2006. doi: 10.1002/humu.23864. Epub 2019 Jul 29.
Empty follicle syndrome (EFS) is a condition in which no oocyte is retrieved from mature follicles after proper ovarian stimulation in an in vitro fertilization procedure. Genetic evidence accumulates for the etiology of recurrent EFS without pharmacological or iatrogenic problems. In this study, we present two infertile sisters in a family with EFS after three cycles of standard ovarian stimulation with human chorionic gonadotrophin and/or gonadotropin-releasing hormone agonist therapy. Via whole-exome sequencing and cosegregation test, we identified compound heterozygous mutations in the gene of ZP1 in both of the infertile sisters. Coimmunoprecipitation tests and homology modeling analysis confirmed that both mutated ZP1 disrupt the formation of oocyte zona pellucida by interrupting the interaction among ZP1, ZP2, and ZP3. We thus propose that the specific mutations in ZP1 gene render a causality for the intractable EFS.
空卵泡综合征（EFS）是指在体外受精过程中，经过适当的卵巢刺激后，从成熟卵泡中未能取出卵母细胞的一种情况。遗传证据逐渐积累，表明在没有药理学或医源性问题的情况下，EFS 会反复发生。在这项研究中，我们介绍了一个家族中的两名不孕姐妹，她们在接受了三个周期的人绒毛膜促性腺激素和/或促性腺激素释放激素激动剂治疗的标准卵巢刺激后出现 EFS。通过全外显子组测序和共分离测试，我们在这两名不孕姐妹中均发现了 ZP1 基因的复合杂合突变。共免疫沉淀试验和同源建模分析证实，这两种突变的 ZP1 通过中断 ZP1、ZP2 和 ZP3 之间的相互作用，破坏了卵母细胞透明带的形成。因此，我们提出 ZP1 基因突变是导致难治性 EFS 的原因。
