University of Oulu

Oura S, Kazi S, Savolainen A, Nozawa K, Castañeda J, Yu Z, et al. (2020) Cfap97d1 is important for flagellar axoneme maintenance and male mouse fertility. PLoS Genet 16(8): e1008954.

Cfap97d1 is important for flagellar axoneme maintenance and male mouse fertility

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Author: Oura, Seiya1; Kazi, Samina2; Savolainen, Audrey2;
Organizations: 1Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
2Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
3Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, United States of America
4Center for Drug Discovery, Baylor College of Medicine, Houston, Texas, United States of America
5Institute of Innate Immunity, Biophysical Imaging, Medical Faculty, University of Bonn, Bonn, Germany
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3 MB)
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Language: English
Published: Public Library of Science, 2020
Publish Date: 2020-12-02


The flagellum is essential for sperm motility and fertilization in vivo. The axoneme is the main component of the flagella, extending through its entire length. An axoneme is comprised of two central microtubules surrounded by nine doublets, the nexin-dynein regulatory complex, radial spokes, and dynein arms. Failure to properly assemble components of the axoneme in a sperm flagellum, leads to fertility alterations. To understand this process in detail, we have defined the function of an uncharacterized gene, Cfap97 domain containing 1 (Cfap97d1). This gene is evolutionarily conserved in mammals and multiple other species, including Chlamydomonas. We have used two independently generated Cfap97d1 knockout mouse models to study the gene function in vivo. Cfap97d1 is exclusively expressed in testes starting from post-natal day 20 and continuing throughout adulthood. Deletion of the Cfap97d1 gene in both mouse models leads to sperm motility defects (asthenozoospermia) and male subfertility. In vitro fertilization (IVF) of cumulus-intact oocytes with Cfap97d1 deficient sperm yielded few embryos whereas IVF with zona pellucida-free oocytes resulted in embryo numbers comparable to that of the control. Knockout spermatozoa showed abnormal motility characterized by frequent stalling in the anti-hook position. Uniquely, Cfap97d1 loss caused a phenotype associated with axonemal doublet heterogeneity linked with frequent loss of the fourth doublet in the sperm stored in the epididymis. This study demonstrates that Cfap97d1 is required for sperm flagellum ultra-structure maintenance, thereby playing a critical role in sperm function and male fertility in mice.

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Series: PLoS genetics
ISSN: 1553-7390
ISSN-E: 1553-7404
ISSN-L: 1553-7390
Volume: 16
Issue: 8
Article number: e1008954
DOI: 10.1371/journal.pgen.1008954
Type of Publication: A1 Journal article – refereed
Field of Science: 1184 Genetics, developmental biology, physiology
Funding: This work was supported by grants from the Academy of Finland ((285151) to R. P-H) and the Sigrid Jusélius Foundation (to R. P-H), a P30 Cancer Center Support Grant (NCI-CA125123, HTAP), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD088412 and P01HD087157 to M.M.M.), and the Bill & Melinda Gates Foundation (INV-001902 to M.M.M.). The Wachten laboratory was supported by grants from the Deutsche Forschungsgemeinschaft (DFG): SPP1926: WA3382/2-1 (to DW), SPP1726: grant WA3382/3-1 (to DW), FOR2743 (to DW), SFB/TRR83 (to DW), and under Germany’s Excellence Strategy – EXC2151 – 390873048 (to DW). Boehringer Ingelheim Fonds (J.N.H.). This work was also supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT)/the Japan Society for the Promotion of Science (JSPS) [KAKENHI grants JP19J21619 (to SO), JP18K14715 and 20K15804 (to JC), JP17H04987 (to HM)]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Academy of Finland Grant Number: 285151
Detailed Information: 285151 (Academy of Finland Funding decision)
Copyright information: © 2020 Oura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.