Single-cell analysis of the aged ovarian immune system reveals a shift towards adaptive immunity and attenuated cell function

  1. Tal Ben Yaakov
  2. Tanya Wasserman
  3. Eliel Aknin
  4. Yonatan Savir  Is a corresponding author
  1. Technion - Israel Institute of Technology, Israel

Abstract

The immune system plays a major role in maintaining many physiological processes in the reproductive system. However, a complete characterization of the immune milieu in the ovary, and particularly how it is affected by female aging, is still lacking. Here, we utilize single-cell RNA sequencing and flow cytometry to construct the complete description of the murine ovarian immune system. We show that the composition of the immune cells undergoes an extensive shift with age towards adaptive immunity. We analyze the effect of aging on gene expression and chemokine and cytokine networks and show an overall decreased expression of inflammatory mediators together with an increased expression of senescent cells recognition receptors. Our results suggest that the fertile female's ovarian immune aging differs from the suggested female post-menopause inflammaging as it copes with the inflammatory stimulations during repeated cycles and the increasing need for clearance of accumulating atretic follicles.

Data availability

All data used in this study are included in the manuscript, the supporting files and in GitHub:https://github.com/SavirLab/AgingOvarianImmuneMilieu

Article and author information

Author details

  1. Tal Ben Yaakov

    Department of Physiology, Biophysics and Systems Biology, Technion - Israel Institute of Technology, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Tanya Wasserman

    Department of Physiology, Biophysics and Systems Biology, Technion - Israel Institute of Technology, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0221-1891
  3. Eliel Aknin

    Department of Physiology, Biophysics and Systems Biology, Technion - Israel Institute of Technology, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Yonatan Savir

    Department of Physiology, Biophysics and Systems Biology, Technion - Israel Institute of Technology, Haifa, Israel
    For correspondence
    yoni.savir@technion.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5345-8491

Funding

Israel Science Foundation (1619/20)

  • Tal Ben Yaakov
  • Tanya Wasserman
  • Eliel Aknin
  • Yonatan Savir

Rappaport Family Institute for Research in the Medical Sciences

  • Tal Ben Yaakov
  • Tanya Wasserman
  • Eliel Aknin
  • Yonatan Savir

Wolfson Foundation

  • Tal Ben Yaakov
  • Tanya Wasserman
  • Eliel Aknin
  • Yonatan Savir

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.This work is supported by the Rappaport Family Institute for Research in the Medical Sciences (YS), the Russell Berrie Nanotechnology Institute (YS), UOM-Israel collaboration (YS), The Wolfson Foundation (YS), ISF grant 1860/21 (RH).

Reviewing Editor

  1. Sara Hägg, Karolinska Institutet, Sweden

Ethics

Animal experimentation: All mouse experiments performed in this study were approved by the Animal Care and UseCommittee of the Technion, Israel Institute of Technology, and found to confirm with theregulations of this Institution for work with laboratory animals, protocol No: IL-069-05-2021.

Version history

  1. Preprint posted: August 13, 2021 (view preprint)
  2. Received: October 21, 2021
  3. Accepted: April 19, 2023
  4. Accepted Manuscript published: April 25, 2023 (version 1)
  5. Version of Record published: May 16, 2023 (version 2)

Copyright

© 2023, Ben Yaakov 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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  1. Tal Ben Yaakov
  2. Tanya Wasserman
  3. Eliel Aknin
  4. Yonatan Savir
(2023)
Single-cell analysis of the aged ovarian immune system reveals a shift towards adaptive immunity and attenuated cell function
eLife 12:e74915.
https://doi.org/10.7554/eLife.74915

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https://doi.org/10.7554/eLife.74915

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