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Alleviation of endoplasmic reticulum stress by tauroursodeoxycholic acid delays senescence of mouse ovarian surface epithelium

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Abstract

Ovarian surface epithelium (OSE) forms a single layer of mostly cuboidal cells on surface of mammalian ovaries that is inherently exposed to cell stress evoked by tissue damage every ovulation and declines morphologically after menopause. Endoplasmic reticulum (ER) is a principal cell organelle involved in proteosynthesis, but also integrating various stress signals. ER stress evokes a conserved signaling pathway, the unfolded protein response (UPR), leading to cell death or adaptation to stress conditions. In this work, we document that mouse OSE suffers from ER stress during replicative senescence in vitro, develops abnormalities in ER and initiates UPR. Attenuation of ER stress in senescent OSE by tauroursodeoxycholic acid (TUDCA) reconditions ER architecture and leads to delayed onset of senescence. In summary, we show for the first time a mutual molecular link between ER stress response and replicative senescence leading to phenotypic changes of non-malignant ovarian surface epithelium.

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Acknowledgements

We acknowledge the core facility CELLIM of CEITEC supported by the Czech-BioImaging large RI project (project no. LM2015062 funded by MEYS CR) for their support with obtaining scientific data presented in this paper.

Funding

This work was supported by the Grant Agency of Masaryk University (project no. MUNI/A/1298/2017) and European Regional Development Fund (Center for Analysis and Modeling of Tissues and Organs, CZ.1.07/2.3.00/20.0185).

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Authors and Affiliations

  1. Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 126/3, 625 00, Brno, Czech Republic

    Kateřina Vašíčková, Lukáš Moráň & Petr Vaňhara

  2. First Department of Pathological Anatomy, St. Anne’s University Hospital Brno, Brno, Pekařská 53, 656 91, Brno, Czech Republic

    Dominik Gurín

Authors
  1. Kateřina Vašíčková
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  2. Lukáš Moráň
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  3. Dominik Gurín
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  4. Petr Vaňhara
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Corresponding author

Correspondence to Petr Vaňhara.

Ethics declarations

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. Animal experiments were supervised by the local ethical committee of the Faculty of Medicine, Masaryk University and performed by certified individuals (KV, PV, and LM). This article does not contain any studies with human participants performed by any of the authors.

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The authors declare that they have no conflict of interest.

Electronic supplementary material

Supplementary Fig. S1

UPR is elicited in intact ovarian explants cultured under ER stress promoting conditions. Dissected ovarian explants were left untreated (a-c) or cultured for 24 h in presence of 0.5 μM tunicamycin (d-f) and processed for immunohistochemistry of HSPA5 and DDIT3. Staining for KRT8 validates intactness of ovarian surface epithelial layer. Scale bars indicate 200 μm (a-c) or 100 μm (d-f) (PNG 2964 kb)

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Vašíčková, K., Moráň, L., Gurín, D. et al. Alleviation of endoplasmic reticulum stress by tauroursodeoxycholic acid delays senescence of mouse ovarian surface epithelium. Cell Tissue Res 374, 643–652 (2018). https://doi.org/10.1007/s00441-018-2888-9

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  • DOI: https://doi.org/10.1007/s00441-018-2888-9

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