Frontiers in Genetics (May 2021)
Case Report: A Novel Heterozygous ZP3 Deletion Associated With Empty Follicle Syndrome and Abnormal Follicular Development
- Yongzhe Chen,
- Yongzhe Chen,
- Zesong Wang,
- Yueren Wu,
- Wenbin He,
- Wenbin He,
- Juan Du,
- Juan Du,
- Juan Du,
- Juan Du,
- Juan Du,
- Sufen Cai,
- Sufen Cai,
- Sufen Cai,
- Sufen Cai,
- Fei Gong,
- Fei Gong,
- Fei Gong,
- Fei Gong,
- Fei Gong,
- Guangxiu Lu,
- Guangxiu Lu,
- Guangxiu Lu,
- Guangxiu Lu,
- Ge Lin,
- Ge Lin,
- Ge Lin,
- Ge Lin,
- Ge Lin,
- Can Dai,
- Can Dai,
- Can Dai
Affiliations
- Yongzhe Chen
- School of Basic Medical Science, Central South University, Changsha, China
- Yongzhe Chen
- National Health Commission Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, China
- Zesong Wang
- Department of Basic Medicine, School of Medicine, Hunan Normal University, Changsha, China
- Yueren Wu
- Department of Basic Medicine, School of Medicine, Hunan Normal University, Changsha, China
- Wenbin He
- Reproductive and Genetic Hospital of China International Trust Investment Corporation Xiangya, Changsha, China
- Wenbin He
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Changsha, China
- Juan Du
- School of Basic Medical Science, Central South University, Changsha, China
- Juan Du
- National Health Commission Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, China
- Juan Du
- Reproductive and Genetic Hospital of China International Trust Investment Corporation Xiangya, Changsha, China
- Juan Du
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Changsha, China
- Juan Du
- National Engineering and Research Center of Human Stem Cell, Changsha, China
- Sufen Cai
- School of Basic Medical Science, Central South University, Changsha, China
- Sufen Cai
- National Health Commission Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, China
- Sufen Cai
- Reproductive and Genetic Hospital of China International Trust Investment Corporation Xiangya, Changsha, China
- Sufen Cai
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Changsha, China
- Fei Gong
- School of Basic Medical Science, Central South University, Changsha, China
- Fei Gong
- National Health Commission Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, China
- Fei Gong
- Reproductive and Genetic Hospital of China International Trust Investment Corporation Xiangya, Changsha, China
- Fei Gong
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Changsha, China
- Fei Gong
- National Engineering and Research Center of Human Stem Cell, Changsha, China
- Guangxiu Lu
- Department of Basic Medicine, School of Medicine, Hunan Normal University, Changsha, China
- Guangxiu Lu
- Reproductive and Genetic Hospital of China International Trust Investment Corporation Xiangya, Changsha, China
- Guangxiu Lu
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Changsha, China
- Guangxiu Lu
- National Engineering and Research Center of Human Stem Cell, Changsha, China
- Ge Lin
- School of Basic Medical Science, Central South University, Changsha, China
- Ge Lin
- National Health Commission Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, China
- Ge Lin
- Reproductive and Genetic Hospital of China International Trust Investment Corporation Xiangya, Changsha, China
- Ge Lin
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Changsha, China
- Ge Lin
- National Engineering and Research Center of Human Stem Cell, Changsha, China
- Can Dai
- Department of Basic Medicine, School of Medicine, Hunan Normal University, Changsha, China
- Can Dai
- Reproductive and Genetic Hospital of China International Trust Investment Corporation Xiangya, Changsha, China
- Can Dai
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Changsha, China
- DOI
- https://doi.org/10.3389/fgene.2021.690070
- Journal volume & issue
-
Vol. 12
Abstract
Background: Empty follicle syndrome (EFS) is defined as the complete failure to retrieve oocytes after ovarian stimulation. Although several mutations in ZP1, ZP2, ZP3, and LHCGR have been identified as genetic causes of EFS, its pathogenesis is still not well-understood.Methods: Whole-exome sequencing (WES) was employed to identify the candidate pathogenic mutations, which were then verified by Sanger sequencing. A study in CHO-K1 cells was performed to analyze the effect of the mutation on protein expression. Additionally, immunohistochemistry (IHC) staining was used to examine follicular development and zona pellucida (ZP) assembly in the ovary of an EFS patient.Results: A novel heterozygous deletion in ZP3 (c.565_579del[p.Thr189_Gly193del]) was identified in the EFS patient. It was inherited dominantly and resulted in significant degradation of the ZP3 protein. Oocytes with degenerated cytoplasm and abnormal ZP assembly were observed in follicles up to the secondary stage, and many empty follicle-like structures were present.Conclusion: We identified a novel ZP3 mutation that expands the mutational spectrum associated with human EFS. We also showed the abnormal follicular development and ZP assembly of the EFS patient with the heterozygous ZP3 mutation, which provides new insights into the pathogenesis of EFS.
Keywords
