Androglobin, a chimeric mammalian globin, is required for male fertility

  1. Anna Keppner
  2. Miguel Correia
  3. Sara Santambrogio
  4. Teng Wei Koay
  5. Darko Maric
  6. Carina Osterhof
  7. Denise V Winter
  8. Angèle Clerc
  9. Michael Stumpe
  10. Frédéric Chalmel
  11. Sylvia Dewilde
  12. Alex Odermatt
  13. Dieter Kressler
  14. Thomas Hankeln
  15. Roland H Wenger
  16. David Hoogewijs  Is a corresponding author
  1. University of Fribourg, Switzerland
  2. University of Zurich, Switzerland
  3. University of Mainz, Germany
  4. University of Basel, Switzerland
  5. University of Rennes, Inserm, UMR_S 1085, France
  6. University of Antwerp, Belgium

Abstract

Spermatogenesis is a highly specialised differentiation process driven by a dynamic gene expression program and ending with the production of mature spermatozoa. Whereas hundreds of genes are known to be essential for male germline proliferation and differentiation, the contribution of several genes remains uncharacterized. The predominant expression of the latest globin family member, androglobin (Adgb), in mammalian testis tissue prompted us to assess its physiological function in spermatogenesis. Adgb knockout mice display male infertility, reduced testis weight, impaired maturation of elongating spermatids, abnormal sperm shape and ultrastructural defects in microtubule and mitochondrial organisation. Epididymal sperm from Adgb knockout animals display multiple flagellar malformations including coiled, bifid or shortened flagella, and erratic acrosomal development. Following immunoprecipitation and mass spectrometry, we could identify septin 10 (Sept10) as interactor of Adgb. The Sept10-Adgb interaction was confirmed both in vivo using testis lysates, and in vitro by reciprocal co-immunoprecipitation experiments. Furthermore, absence of Adgb leads to mislocalisation of Sept10 in sperm, indicating defective manchette and sperm annulus formation. Finally, in vitro data suggest that Adgb contributes to Sept10 proteolysis in a calmodulin (CaM)-dependent manner. Collectively, our results provide evidence that Adgb is essential for murine spermatogenesis and further suggest that Adgb is required for sperm head shaping via the manchette and proper flagellum formation.

Data availability

RNA-sequencing data have been submitted to ENA with accession number PRJEB46499 and is also available as supplemental dataset 1 (excel table).All data generated or analysed during this study are included in the manuscript and supporting files. Source data files are provided for Figures 1, 2, 4B, 4C, 4D, 4E, 6A, 6B, 6C, 6D, 6E, 6F, Fig. 1-fig. suppl. 1, Fig. 4-fig. suppl. 1A, B, C, D, E, F, G, Fig. 4-fig. suppl. 2A, B, C, Fig. 4-fig. suppl. 3A, B, C, D, E, Fig. 4-fig. suppl. 5, Fig. 4-fig. suppl. 6B, Fig. 6-fig. suppl. 1A, Fig. 6-fig. suppl. 4, Fig. 6-fig. suppl. 5D, E.

Article and author information

Author details

  1. Anna Keppner

    Department of Endocrinology, Metabolism and Cardiovascular system, University of Fribourg, Fribourg, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Miguel Correia

    Department of Endocrinology, Metabolism and Cardiovascular system, University of Fribourg, Fribourg, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Sara Santambrogio

    Institute of Physiology, University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Teng Wei Koay

    Department of Endocrinology, Metabolism and Cardiovascular system, University of Fribourg, Fribourg, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Darko Maric

    Department of Endocrinology, Metabolism and Cardiovascular system, University of Fribourg, Fribourg, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Carina Osterhof

    Institute for Organismic and Molecular Evolutionary Biology, University of Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1699-7410
  7. Denise V Winter

    Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  8. Angèle Clerc

    Department of Endocrinology, Metabolism and Cardiovascular system, University of Fribourg, Fribourg, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  9. Michael Stumpe

    Department of Biology, University of Fribourg, Fribourg, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9443-9326
  10. Frédéric Chalmel

    University of Rennes, Inserm, UMR_S 1085, Rennes, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Sylvia Dewilde

    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  12. Alex Odermatt

    Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  13. Dieter Kressler

    Department of Biology, University of Fribourg, Fribourg, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4855-3563
  14. Thomas Hankeln

    Institute for Organismic and Molecular Evolutionary Biology, University of Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  15. Roland H Wenger

    Institute of Physiology, University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  16. David Hoogewijs

    Department of Endocrinology, Metabolism and Cardiovascular system, University of Fribourg, Fribourg, Switzerland
    For correspondence
    david.hoogewijs@unifr.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5547-6004

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_173000)

  • David Hoogewijs

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030_207460)

  • David Hoogewijs

Deutsche Forschungsgemeinschaft (HO 5837/1-1)

  • David Hoogewijs

Deutsche Forschungsgemeinschaft (HA 2103/9-1)

  • Thomas Hankeln

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experimental procedures and animal maintenance followed Swiss federal guidelines and the study was revised and approved by the "Service de la sécurité alimentaire et des affaires vétérinaires" (SAAV) of the canton of Fribourg, Switzerland (license number 2017_16_FR).

Reviewing Editor

  1. T Rajendra Kumar, University of Colorado, United States

Publication history

  1. Received: July 21, 2021
  2. Accepted: June 13, 2022
  3. Accepted Manuscript published: June 14, 2022 (version 1)

Copyright

© 2022, Keppner et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Anna Keppner
  2. Miguel Correia
  3. Sara Santambrogio
  4. Teng Wei Koay
  5. Darko Maric
  6. Carina Osterhof
  7. Denise V Winter
  8. Angèle Clerc
  9. Michael Stumpe
  10. Frédéric Chalmel
  11. Sylvia Dewilde
  12. Alex Odermatt
  13. Dieter Kressler
  14. Thomas Hankeln
  15. Roland H Wenger
  16. David Hoogewijs
(2022)
Androglobin, a chimeric mammalian globin, is required for male fertility
eLife 11:e72374.
https://doi.org/10.7554/eLife.72374

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