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The sperm protein SPACA4 is required for efficient fertilization in mice

Sarah Herberg, View ORCID ProfileYoshitaka Fujihara, Andreas Blaha, Karin Panser, Kiyonori Kobayashi, Tamara Larasati, Maria Novatchkova, H. Christian Theußl, Olga Olszanska, View ORCID ProfileMasahito Ikawa, View ORCID ProfileAndrea Pauli
doi: https://doi.org/10.1101/2021.05.02.442348
Sarah Herberg
1Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria
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Yoshitaka Fujihara
2Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
3Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, Suita, Osaka 564-8565, Japan
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Andreas Blaha
1Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria
4Vienna BioCenter PhD Program, Doctoral School of the University at Vienna and Medical University of Vienna, Vienna, Austria
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Karin Panser
1Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria
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Kiyonori Kobayashi
2Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
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Tamara Larasati
2Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
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Maria Novatchkova
1Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria
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H. Christian Theußl
1Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria
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Olga Olszanska
1Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria
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Masahito Ikawa
2Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
5Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
6Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
7The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
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  • For correspondence: ikawa@biken.osaka-u.ac.jp andrea.pauli@imp.ac.at
Andrea Pauli
1Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria
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  • For correspondence: ikawa@biken.osaka-u.ac.jp andrea.pauli@imp.ac.at
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SUMMARY

Fertilization is the fundamental process that initiates the development of a new individual in all sexually reproducing species. Despite its importance, our understanding of the molecular players that govern mammalian sperm-egg interaction is incomplete, partly because many of the essential factors found in non-mammalian species do not have obvious mammalian homologs. We have recently identified the Ly6/uPAR protein Bouncer as a new, essential fertilization factor in zebrafish (Herberg et al., 2018). Here, we show that Bouncer’s homolog in mammals, SPACA4, is also required for efficient fertilization in mice. In contrast to fish, where Bouncer is expressed specifically in the egg, SPACA4 is expressed exclusively in the sperm. Male knockout mice are severely sub-fertile, and sperm lacking SPACA4 fail to fertilize wild-type eggs in vitro. Interestingly, removal of the zona pellucida rescues the fertilization defect of Spaca4-deficient sperm in vitro, indicating that SPACA4 is not required for the interaction of sperm and the oolemma but rather of sperm and zona pellucida. Our work identifies SPACA4 as an important sperm protein necessary for zona pellucida penetration during mammalian fertilization.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 04, 2021.
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The sperm protein SPACA4 is required for efficient fertilization in mice
Sarah Herberg, Yoshitaka Fujihara, Andreas Blaha, Karin Panser, Kiyonori Kobayashi, Tamara Larasati, Maria Novatchkova, H. Christian Theußl, Olga Olszanska, Masahito Ikawa, Andrea Pauli
bioRxiv 2021.05.02.442348; doi: https://doi.org/10.1101/2021.05.02.442348
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The sperm protein SPACA4 is required for efficient fertilization in mice
Sarah Herberg, Yoshitaka Fujihara, Andreas Blaha, Karin Panser, Kiyonori Kobayashi, Tamara Larasati, Maria Novatchkova, H. Christian Theußl, Olga Olszanska, Masahito Ikawa, Andrea Pauli
bioRxiv 2021.05.02.442348; doi: https://doi.org/10.1101/2021.05.02.442348

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