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Mutations in ZP4 are associated with abnormal zona pellucida and female infertility
  1. Xiaoli Wei1,
  2. Youzhu Li2,
  3. Qicai Liu3,
  4. Wensheng Liu1,
  5. Xiaohong Yan2,
  6. Xingshen Zhu1,
  7. Dekun Zhou1,
  8. Yingpu Tian1,
  9. Fuxing Zhang4,
  10. Na Li5,
  11. Zhongxian Lu1
  1. 1School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China
  2. 2Reproductive Medicine Center, the First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
  3. 3Center for Reproductive Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
  4. 4Department of General Surgery, the First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
  5. 5Intensive Care Unit, Fujian Medical University Xiamen Humanity Hospital, Xiamen, China
  1. Correspondence to Dr Zhongxian Lu, School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen 361005, Fujian, China; zhongxian{at}xmu.edu.cn; Dr Na Li, Intensive Care Unit, Fujian Medical University Xiamen Humanity Hospital, Xiamen, China; lengyuecc{at}sina.com; Dr Fuxing Zhang, Department of General Surgery, the First Affiliated Hospital of Xiamen University, Xiamen, China; zhangfuxing{at}medmail.com.cn

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.

  • ovary
  • pathology
  • molecular
  • cell biology
  • DNA

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Footnotes

  • 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.

  • Patient consent for publication Obtained.

  • Ethics approval This study was approved by the ethics committees of the First Affiliated Hospital of Xiamen University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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