Mutations in <i>ZP4</i> are associated with abnormal zona pellucida and female infertility
Xiaoli Wei, Youzhu Li, Qicai Liu, Wensheng Liu, Xiaohong Yan, Xingshen Zhu, Dekun Zhou, Yingpu Tian, Fu-Xing Zhang, Na Li, Zhongxian Lu
Abstract
Background The zona pellucida (ZP) of human oocytes plays essential protective roles in sperm–egg interactions during fertilisation and embryo development. ZP4 -null female rabbits exhibit a thin and irregular ZP, which severely impairs embryo development and fertility. However, the effects of ZP4 defect on human female reproduction remain unknown. Methods and results We performed whole-exome sequencing in 26 female patients with abnormal (thin and irregular) ZP and identified heterozygous variants in ZP4 (OMIM: 613514) from 3 patients (approximately 11%). No ZP4 variant was found in the 30 control women with proven fertility. We constructed ZP4- mutated plasmids and found that the variants reduced the secretion of ZP4 in vitro. Lower suction pressure facilitated egg retrieval, and intracytoplasmic sperm injection (ICSI) was a desirable treatment for ZP4- mutated patients with abnormal ZP. Conclusions We identified ZP4 as a novel gene for human abnormal ZP and found that lower suction pressure and ICSI are efficient treatment strategies.