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    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. 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. We identified ZP4 as a novel gene for human abnormal ZP and found that lower suction pressure and ICSI are efficient treatment strategies. © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

    Citation

    Xiaoli Wei, Youzhu Li, Qicai Liu, Wensheng Liu, Xiaohong Yan, Xingshen Zhu, Dekun Zhou, Yingpu Tian, Fuxing Zhang, Na Li, Zhongxian Lu. Mutations in ZP4 are associated with abnormal zona pellucida and female infertility. Journal of clinical pathology. 2022 Mar;75(3):201-204

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    PMID: 33461974

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