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.
- cell biology
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Handling editor Mona El-Bahrawy.
XW, YL and QL contributed equally.
Contributors ZL, NL and FZ conceived this study and revised the manuscript; YL and QL recruited the participants and performed in silico analyses; XW and WL conducted the data analysis and wrote the manuscript; XY collected blood samples and the clinical data; XZ, DZ and YT conducted molecular experiments and data analyses. All authors approved the final manuscript.
Funding This work was supported by the Natural Science Foundation of Fujian Province of China (Grant No. 2019J01565),the Medical and Health Guidance Project of Xiamen (Grant No.3502Z20209267), and the National Key R&D Program of China (No. SQ2017YFSF080005-02).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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