TMEM95 is a sperm membrane protein essential for mammalian fertilization
Abstract
The fusion of gamete membranes during fertilization is an essential process for sexual reproduction. Despite its importance, only three proteins are known to be indispensable for sperm-egg membrane fusion: the sperm proteins IZUMO1 and SPACA6, and the egg protein JUNO. Here we demonstrate that another sperm protein, TMEM95, is necessary for sperm-egg interaction. TMEM95 ablation in mice caused complete male-specific infertility. Sperm lacking this protein were morphologically normal exhibited normal motility, and could penetrate the zona pellucida and bind to the oolemma. However, once bound to the oolemma, TMEM95-deficient sperm were unable to fuse with the egg membrane or penetrate into the ooplasm, and fertilization could only be achieved by mechanical injection of one sperm into the ooplasm, thereby bypassing membrane fusion. These data demonstrate that TMEM95 is essential for mammalian fertilization.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Ministerio de Economía y Competitividad (RYC-2012-10193)
- Pablo Bermejo-Álvarez
Ministerio de Economía y Competitividad (FPI fellowship)
- Ismael Lamas-Toranzo
Ministerio de Economía y Competitividad (Ramón y Cajal contract)
- Serafín Pérez-Cerezales
European Union Seventh Framework Programme (Marie Curie fellowship)
- Beatriz Fernández-Fuertes
Medical Research Council (MR/M012468/1)
- Enrica Bianchi
- Gavin J Wright
Ministerio de Economía y Competitividad (AGL2014-58739-R)
- Pablo Bermejo-Álvarez
Ministerio de Economía y Competitividad (AGL2017-84908-R)
- Pablo Bermejo-Álvarez
Ministerio de Economía y Competitividad (AGL2015-70159-P)
- María Jiménez-Movilla
Ministerio de Economía y Competitividad (RTI2018-093548-B-I00)
- Alfonso Gutiérrez-Adán
Ministerio de Economía y Competitividad (AGL2016-71890-REDT)
- Alfonso Gutiérrez-Adán
- María Jiménez-Movilla
- Pablo Bermejo-Álvarez
H2020 European Research Council (StG 757886-ELONGAN)
- Pablo Bermejo-Álvarez
Fundación Séneca-Agencia de Ciencia y Tecnología de Murcia (20887/PI/18)
- María Jiménez-Movilla
Department of Agriculture, Food and the Marine (11/S/104)
- Pat Lonergan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Polina V Lishko, University of California, Berkeley, United States
Ethics
Animal experimentation: All experimental procedures were approved by INIA Animal Care Committee and Madrid Region Authorities (PROEX 040/17) in agreement with European legislation.
Version history
- Received: November 24, 2019
- Accepted: June 1, 2020
- Accepted Manuscript published: June 2, 2020 (version 1)
- Version of Record published: June 15, 2020 (version 2)
Copyright
© 2020, Lamas-Toranzo 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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