TMEM95 is a sperm membrane protein essential for mammalian fertilization

  1. Ismael Lamas-Toranzo
  2. Julieta G Hamze
  3. Enrica Bianchi
  4. Beatriz Fernández-Fuertes
  5. Serafín Pérez-Cerezales
  6. Ricardo Laguna-Barraza
  7. Raúl Fernández-González
  8. Pat Lonergan
  9. Alfonso Gutiérrez-Adán
  10. Gavin J Wright
  11. María Jiménez-Movilla  Is a corresponding author
  12. Pablo Bermejo-Álvarez  Is a corresponding author
  1. INIA, Spain
  2. University of Murcia, Spain
  3. Wellcome Trust Sanger Institute, United Kingdom
  4. University of Girona, Spain
  5. University College Dublin, Ireland

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

  1. Ismael Lamas-Toranzo

    Animal Reproduction, INIA, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7790-2649
  2. Julieta G Hamze

    Department of Cell Biology and Histology, University of Murcia, Murcia, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Enrica Bianchi

    Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Beatriz Fernández-Fuertes

    Department of Biology, University of Girona, Girona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Serafín Pérez-Cerezales

    Animal Reproduction, INIA, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  6. Ricardo Laguna-Barraza

    Animal Reproduction, INIA, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Raúl Fernández-González

    Animal Reproduction, INIA, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  8. Pat Lonergan

    School of Agriculture and Food Science, University College Dublin, Dublin, Ireland
    Competing interests
    The authors declare that no competing interests exist.
  9. Alfonso Gutiérrez-Adán

    Animal Reproduction, INIA, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  10. Gavin J Wright

    Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0537-0863
  11. María Jiménez-Movilla

    Department of Cell Biology and Histology, University of Murcia, Murcia, Spain
    For correspondence
    mariajm@um.es
    Competing interests
    The authors declare that no competing interests exist.
  12. Pablo Bermejo-Álvarez

    Animal Reproduction, INIA, Madrid, Spain
    For correspondence
    bermejo.pablo@inia.es
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9907-2626

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

  1. 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

  1. Received: November 24, 2019
  2. Accepted: June 1, 2020
  3. Accepted Manuscript published: June 2, 2020 (version 1)
  4. 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.

Metrics

  • 4,940
    views
  • 654
    downloads
  • 80
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Ismael Lamas-Toranzo
  2. Julieta G Hamze
  3. Enrica Bianchi
  4. Beatriz Fernández-Fuertes
  5. Serafín Pérez-Cerezales
  6. Ricardo Laguna-Barraza
  7. Raúl Fernández-González
  8. Pat Lonergan
  9. Alfonso Gutiérrez-Adán
  10. Gavin J Wright
  11. María Jiménez-Movilla
  12. Pablo Bermejo-Álvarez
(2020)
TMEM95 is a sperm membrane protein essential for mammalian fertilization
eLife 9:e53913.
https://doi.org/10.7554/eLife.53913

Share this article

https://doi.org/10.7554/eLife.53913

Further reading

    1. Cell Biology
    2. Developmental Biology
    Corey D Holman, Alexander P Sakers ... Patrick Seale
    Research Article

    The energy-burning capability of beige adipose tissue is a potential therapeutic tool for reducing obesity and metabolic disease, but this capacity is decreased by aging. Here, we evaluate the impact of aging on the profile and activity of adipocyte stem and progenitor cells (ASPCs) and adipocytes during the beiging process in mice. We found that aging increases the expression of Cd9 and other fibro-inflammatory genes in fibroblastic ASPCs and blocks their differentiation into beige adipocytes. Fibroblastic ASPC populations from young and aged mice were equally competent for beige differentiation in vitro, suggesting that environmental factors suppress adipogenesis in vivo. Examination of adipocytes by single nucleus RNA-sequencing identified compositional and transcriptional differences in adipocyte populations with aging and cold exposure. Notably, cold exposure induced an adipocyte population expressing high levels of de novo lipogenesis (DNL) genes, and this response was severely blunted in aged animals. We further identified Npr3, which encodes the natriuretic peptide clearance receptor, as a marker gene for a subset of white adipocytes and an aging-upregulated gene in adipocytes. In summary, this study indicates that aging blocks beige adipogenesis and dysregulates adipocyte responses to cold exposure and provides a resource for identifying cold and aging-regulated pathways in adipose tissue.

    1. Cell Biology
    Tongtong Ma, Ruimin Ren ... Heng Wang
    Research Article

    Current studies on cultured meat mainly focus on the muscle tissue reconstruction in vitro, but lack the formation of intramuscular fat, which is a crucial factor in determining taste, texture, and nutritional contents. Therefore, incorporating fat into cultured meat is of superior value. In this study, we employed the myogenic/lipogenic transdifferentiation of chicken fibroblasts in 3D to produce muscle mass and deposit fat into the same cells without the co-culture or mixture of different cells or fat substances. The immortalized chicken embryonic fibroblasts were implanted into the hydrogel scaffold, and the cell proliferation and myogenic transdifferentiation were conducted in 3D to produce the whole-cut meat mimics. Compared to 2D, cells grown in 3D matrix showed elevated myogenesis and collagen production. We further induced fat deposition in the transdifferentiated muscle cells and the triglyceride content could be manipulated to match and exceed the levels of chicken meat. The gene expression analysis indicated that both lineage-specific and multifunctional signalings could contribute to the generation of muscle/fat matrix. Overall, we were able to precisely modulate muscle, fat, and extracellular matrix contents according to balanced or specialized meat preferences. These findings provide new avenues for customized cultured meat production with desired intramuscular fat contents that can be tailored to meet the diverse demands of consumers.