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Novel mutations in DNAH17 cause sperm flagellum defects and their influence on ICSI outcome

  • Gamete Biology
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To identify new mutations in DNAH17 that cause male infertility and analyze intracytoplasmic sperm injection (ICSI) outcomes in patients with DNAH17 mutations.

Methods

A total of five cases of new DNAH17 mutations exhibiting the multiple morphological abnormalities of the sperm flagella (MMAF) phenotype were identified through semen analysis and genetic testing. They were recruited at our reproductive medicine center from September 2018 to July 2022. Information on DNAH17 genetic mutations and ICSI outcomes was systematically explored following a literature review.

Results

Three novel compound mutations in DNAH17 were identified in patients with male infertility caused by MMAF. This study and previous publications included 21 patients with DNAH17 mutations. DNAH17 has been associated with asthenozoospermia and male infertility, but different types of DNAH17 variants appear to be involved in different sperm phenotypes. In 11 couples of infertile patients with DNAH17 mutations, there were 17 ICSI cycles and 13 embryo transplantation cycles. Only three men with DNAH17 variants ultimately achieved clinical pregnancy with their partners through ICSI combined with assisted oocyte activation (AOA).

Conclusions

Loss-of-function mutations in DNAH17 can lead to severe sperm flagellum defects and male infertility. Patients with MMAF-harboring DNAH17 mutations generally have worse pregnancy outcomes following ICSI. ICSI combined with AOA may improve the outcome of assisted reproductive techniques (ARTs) for men with DNAH17 variants.

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Data availability

Data are available upon reasonable request.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (82101682) and Key research and development plan of Anhui Province (202004j07020032).

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Author notes

  1. Bing Song, Tianjin Yang, Qunshan Shen and Yiyuan Liu contributed equally to this work.

Authors and Affiliations

  1. Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China

    Bing Song, Tianjin Yang, Qunshan Shen, Yiyuan Liu, Chao Wang, Guanjian Li, Yang Gao, Yunxia Cao & Xiaojin He

  2. NHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei, 230032, China

    Bing Song, Qunshan Shen, Chao Wang, Guanjian Li, Yang Gao, Yunxia Cao & Xiaojin He

  3. Ministry of Education Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Hefei, 230032, China

    Bing Song, Qunshan Shen, Chao Wang, Guanjian Li, Yang Gao, Yunxia Cao & Xiaojin He

  4. Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, 230032, China

    Bing Song, Qunshan Shen, Chao Wang, Guanjian Li, Yang Gao, Yunxia Cao & Xiaojin He

  5. Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, 230032, China

    Bing Song, Qunshan Shen, Chao Wang, Guanjian Li, Yang Gao, Yunxia Cao & Xiaojin He

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  1. Bing Song
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Corresponding authors

Correspondence to Yunxia Cao or Xiaojin He.

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Ethics approval and consent to participate

This study was approved by the Ethical Review Board of The First Affiliated Hospital of Anhui Medical University and was conducted according to the Declaration of Helsinki principles. Written informed consents were obtained from all enrolled patients.

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The authors declare no competing interests.

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Song, B., Yang, T., Shen, Q. et al. Novel mutations in DNAH17 cause sperm flagellum defects and their influence on ICSI outcome. J Assist Reprod Genet 40, 2485–2492 (2023). https://doi.org/10.1007/s10815-023-02897-7

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  • DOI: https://doi.org/10.1007/s10815-023-02897-7

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