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Sperm membrane proteins DCST1 and DCST2 are required for the sperm-egg fusion process in mice and fish

View ORCID ProfileTaichi Noda, View ORCID ProfileAndreas Blaha, View ORCID ProfileYoshitaka Fujihara, View ORCID ProfileKrista R. Gert, View ORCID ProfileChihiro Emori, View ORCID ProfileVictoria E. Deneke, View ORCID ProfileSeiya Oura, View ORCID ProfileSara Berent, Mayo Kodani, Karin Panser, Luis Enrique Cabrera-Quio, View ORCID ProfileAndrea Pauli, View ORCID ProfileMasahito Ikawa
doi: https://doi.org/10.1101/2021.04.18.440256
Taichi Noda
1Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
2Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
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Andreas Blaha
3Research 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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Yoshitaka Fujihara
1Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
5Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan
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Krista R. Gert
3Research 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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Chihiro Emori
1Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
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Victoria E. Deneke
3Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria
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Seiya Oura
1Research Institute for Microbial Diseases, 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
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Sara Berent
3Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria
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Mayo Kodani
1Research Institute for Microbial Diseases, 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
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Karin Panser
3Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria
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Luis Enrique Cabrera-Quio
3Research 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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Andrea Pauli
3Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria
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  • For correspondence: [email protected] [email protected]
Masahito Ikawa
1Research Institute for Microbial Diseases, 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: [email protected] [email protected]
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Abstract

The process of sperm-egg fusion is critical for successful fertilization, yet the underlying mechanisms that regulate these steps have remained unclear in vertebrates. Here, we show that both mouse and zebrafish DCST1 and DCST2 are necessary in sperm to fertilize the egg, similar to their orthologs SPE-42 and SPE-49 in C. elegans and Sneaky in D. melanogaster. Mouse Dcst1 and Dcst2 single knockout (KO) spermatozoa are able to undergo the acrosome reaction and show normal relocalization of IZUMO1, an essential factor for sperm-egg fusion, to the equatorial segment. While both single KO spermatozoa can bind to the oolemma, they rarely fuse with oocytes, resulting in male sterility. Similar to mice, zebrafish dcst1 KO males are subfertile and dcst2 and dcst1/2 double KO males are sterile. Zebrafish dcst1/2 KO spermatozoa are motile and can approach the egg, but rarely bind to the oolemma. These data demonstrate that DCST1/2 are essential for male fertility in two vertebrate species, highlighting their crucial role as conserved factors in 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 4.0 International license.
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Posted May 03, 2021.
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Sperm membrane proteins DCST1 and DCST2 are required for the sperm-egg fusion process in mice and fish
Taichi Noda, Andreas Blaha, Yoshitaka Fujihara, Krista R. Gert, Chihiro Emori, Victoria E. Deneke, Seiya Oura, Sara Berent, Mayo Kodani, Karin Panser, Luis Enrique Cabrera-Quio, Andrea Pauli, Masahito Ikawa
bioRxiv 2021.04.18.440256; doi: https://doi.org/10.1101/2021.04.18.440256
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Sperm membrane proteins DCST1 and DCST2 are required for the sperm-egg fusion process in mice and fish
Taichi Noda, Andreas Blaha, Yoshitaka Fujihara, Krista R. Gert, Chihiro Emori, Victoria E. Deneke, Seiya Oura, Sara Berent, Mayo Kodani, Karin Panser, Luis Enrique Cabrera-Quio, Andrea Pauli, Masahito Ikawa
bioRxiv 2021.04.18.440256; doi: https://doi.org/10.1101/2021.04.18.440256

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