PT  - JOURNAL ARTICLE
AU  - Xiaoli Wei
AU  - Youzhu Li
AU  - Qicai Liu
AU  - Wensheng Liu
AU  - Xiaohong Yan
AU  - Xingshen Zhu
AU  - Dekun Zhou
AU  - Yingpu Tian
AU  - Fuxing Zhang
AU  - Na Li
AU  - Zhongxian Lu
TI  - Mutations in <em>ZP4</em> are associated with abnormal zona pellucida and female infertility
AID  - 10.1136/jclinpath-2020-207170
DP  - 2022 Mar 01
TA  - Journal of Clinical Pathology
PG  - 201--204
VI  - 75
IP  - 3
4099  - http://jcp.bmj.com/content/75/3/201.short
4100  - http://jcp.bmj.com/content/75/3/201.full
SO  - J Clin Pathol2022 Mar 01; 75
AB  - 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.