IQCN disruption causes fertilization failure and male infertility due to manchette assembly defect
Abstract Total fertilization failure (TFF) is an important cause of infertility; however, the genetic basis of TFF caused by male factors remains to be clarified. In this study, whole‐exome sequencing was firstly used to screen for genetic causes of TFF after intracytoplasmic sperm injection (ICSI),...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2022-12-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202216501 |
| _version_ | 1797285762922708992 |
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| author | Jing Dai Qi Li Qinwei Zhou Shen Zhang Junru Chen Yize Wang Jing Guo Yifan Gu Fei Gong Yueqiu Tan Guangxiu Lu Wei Zheng Ge Lin |
| author_facet | Jing Dai Qi Li Qinwei Zhou Shen Zhang Junru Chen Yize Wang Jing Guo Yifan Gu Fei Gong Yueqiu Tan Guangxiu Lu Wei Zheng Ge Lin |
| author_sort | Jing Dai |
| collection | DOAJ |
| description | Abstract Total fertilization failure (TFF) is an important cause of infertility; however, the genetic basis of TFF caused by male factors remains to be clarified. In this study, whole‐exome sequencing was firstly used to screen for genetic causes of TFF after intracytoplasmic sperm injection (ICSI), and homozygous variants in the novel gene IQ motif‐containing N (IQCN) were identified in two affected individuals with abnormal acrosome structures. Then, Iqcn‐knockout mice were generated by CRISPR‐Cas9 technology and showed that the knockout male mice resembled the human phenotypes. Additionally, we found that IQCN regulates microtubule nucleation during manchette assembly via calmodulin and related calmodulin‐binding proteins, which resulted in head deformity with aberrant oocyte activation factor PLCζ. Fortunately, ICSI with assisted oocyte activation can overcome IQCN‐associate TFF and male infertility. Thus, our study firstly identified the function of IQCN, highlights the relationship between the manchette assembly and fertilization, and provides a genetic marker and a therapeutic option for male‐source TFF. |
| first_indexed | 2024-03-07T18:06:59Z |
| format | Article |
| id | doaj.art-d9ec0031a3e447519d49c8661000c023 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T18:06:59Z |
| publishDate | 2022-12-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-d9ec0031a3e447519d49c8661000c0232024-03-02T08:44:39ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842022-12-011412n/an/a10.15252/emmm.202216501IQCN disruption causes fertilization failure and male infertility due to manchette assembly defectJing Dai0Qi Li1Qinwei Zhou2Shen Zhang3Junru Chen4Yize Wang5Jing Guo6Yifan Gu7Fei Gong8Yueqiu Tan9Guangxiu Lu10Wei Zheng11Ge Lin12Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science Central South University ChangSha ChinaReproductive Medicine Center, Xiangya Hospital Central South University ChangSha ChinaReproductive and Genetic Hospital of CITIC‐XIANGYA ChangSha ChinaReproductive and Genetic Hospital of CITIC‐XIANGYA ChangSha ChinaReproductive and Genetic Hospital of CITIC‐XIANGYA ChangSha ChinaInstitute of Reproductive and Stem Cell Engineering, School of Basic Medical Science Central South University ChangSha ChinaReproductive and Genetic Hospital of CITIC‐XIANGYA ChangSha ChinaInstitute of Reproductive and Stem Cell Engineering, School of Basic Medical Science Central South University ChangSha ChinaInstitute of Reproductive and Stem Cell Engineering, School of Basic Medical Science Central South University ChangSha ChinaInstitute of Reproductive and Stem Cell Engineering, School of Basic Medical Science Central South University ChangSha ChinaReproductive and Genetic Hospital of CITIC‐XIANGYA ChangSha ChinaReproductive and Genetic Hospital of CITIC‐XIANGYA ChangSha ChinaInstitute of Reproductive and Stem Cell Engineering, School of Basic Medical Science Central South University ChangSha ChinaAbstract Total fertilization failure (TFF) is an important cause of infertility; however, the genetic basis of TFF caused by male factors remains to be clarified. In this study, whole‐exome sequencing was firstly used to screen for genetic causes of TFF after intracytoplasmic sperm injection (ICSI), and homozygous variants in the novel gene IQ motif‐containing N (IQCN) were identified in two affected individuals with abnormal acrosome structures. Then, Iqcn‐knockout mice were generated by CRISPR‐Cas9 technology and showed that the knockout male mice resembled the human phenotypes. Additionally, we found that IQCN regulates microtubule nucleation during manchette assembly via calmodulin and related calmodulin‐binding proteins, which resulted in head deformity with aberrant oocyte activation factor PLCζ. Fortunately, ICSI with assisted oocyte activation can overcome IQCN‐associate TFF and male infertility. Thus, our study firstly identified the function of IQCN, highlights the relationship between the manchette assembly and fertilization, and provides a genetic marker and a therapeutic option for male‐source TFF.https://doi.org/10.15252/emmm.202216501calmodulinfertilization failureIQCNmanchettePLCζ |
| spellingShingle | Jing Dai Qi Li Qinwei Zhou Shen Zhang Junru Chen Yize Wang Jing Guo Yifan Gu Fei Gong Yueqiu Tan Guangxiu Lu Wei Zheng Ge Lin IQCN disruption causes fertilization failure and male infertility due to manchette assembly defect EMBO Molecular Medicine calmodulin fertilization failure IQCN manchette PLCζ |
| title | IQCN disruption causes fertilization failure and male infertility due to manchette assembly defect |
| title_full | IQCN disruption causes fertilization failure and male infertility due to manchette assembly defect |
| title_fullStr | IQCN disruption causes fertilization failure and male infertility due to manchette assembly defect |
| title_full_unstemmed | IQCN disruption causes fertilization failure and male infertility due to manchette assembly defect |
| title_short | IQCN disruption causes fertilization failure and male infertility due to manchette assembly defect |
| title_sort | iqcn disruption causes fertilization failure and male infertility due to manchette assembly defect |
| topic | calmodulin fertilization failure IQCN manchette PLCζ |
| url | https://doi.org/10.15252/emmm.202216501 |
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