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Human Amnion Membrane-Derived Mesenchymal Stem Cells and Conditioned Medium Can Ameliorate X-Irradiation-Induced Testicular Injury by Reducing Endoplasmic Reticulum Stress and Apoptosis

  • Regenerative Medicine: Original Article
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Abstract

Today, infertility affects 15% of couples and half of this rate is due to reproductive problems in men. Radiation-induced damage to the testicles causes sterility depending on the dose. Radiation causes endoplasmic reticulum (ER) stress and ER stress induces apoptosis. In this study, the effect of human amniotic membrane-derived mesenchymal stem cells (hAMSCs) and conditioned medium (hAMSCs-CM) on testicular damage induced by ionizing radiation is aimed to be elucidated through ER stress and apoptosis mechanisms. Six gray scrotal irradiation was used to create a testicular injury model. hAMSCs isolated and characterized with immunofluorescence and flow cytometry, while 2.5 × 105 hAMSCs were transplanted into testis and hAMSCs-CM was applied. Fertility assessment was performed. Expressions of ER stress markers GRP78, Ire1, Chop and Caspase-12, and Caspase-3 were determined. TUNEL was performed. Serum FSH, LH, and testosterone were measured. After hAMSC transplantation and administration of hAMSCs-CM, offsprings were obtained. Seminiferous tubule diameter and seminiferous epithelial height increased. The expression of GRP78, IRE1α, CHOP, Caspase-12, and Caspase-3 decreased. Percentages of tunel positive cells decreased. While FSH and LH levels decreased, testosterone increased. After irradiation, both hAMSCs transplantation and paracrine activity of hAMSCs may have a role in reducing ER stress by suppressing the UPR response. Decrease in FSH and LH and increase in testosterone level after MSCs transplantation may have contributed to the improvement of spermatogenesis. Thus, it can be said that MSCs derived from human amniotic membrane can improve ionized radiation-induced testicular damage by reducing ER stress and apoptosis.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This study was supported by Research Foundation of Zonguldak Bulent Ecevit University, Turkey (project number: 2018–98210206-03).

Author information

Authors and Affiliations

  1. Department of Histology and Embryology, Medicine Faculty, Zonguldak Bulent Ecevit University, Zonguldak, Turkey

    Busra Cetinkaya-Un & Meryem Akpolat

  2. Department of Gynecology and Obstetrics, University of Health Sciences Adana City Training and Research Hospital, Adana, Turkey

    Burak Un

  3. Department of Radiation Oncology, Medicine Faculty, Cukurova University, Adana, Turkey

    Fundagul Andic

  4. Department of Histology and Embryology, Medicine Faculty, Kocaeli University, Kocaeli, Turkey

    Yusufhan Yazir

Authors
  1. Busra Cetinkaya-Un
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  2. Burak Un
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  4. Fundagul Andic
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  5. Yusufhan Yazir
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Contributions

Busra Cetinkaya-Un: conceptualization, methodology, validation, investigation, data collection, writing.

Burak Un: investigation, data collection.

Meryem Akpolat: conceptualization, methodology, validation, control, supervisor.

Fundagul Andic: creation of rat testicular injury model.

Yusufhan Yazır: control, supervisor.

Corresponding author

Correspondence to Busra Cetinkaya-Un.

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Ethics Approval

This study was approved by Zonguldak Bulent Ecevit University Clinical Research Ethics Committee (File number: 2018-188-12/09) and was conducted in accordance with the principles of the Helsinki Declaration.

The study was approved by the Animal Care and Use Committee of Cukurova University (File number 2018.07.2019/06) and followed the guidelines of the International Association for the Study of Pain.

Conflict of Interest

The authors declare no competing interests.

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Cetinkaya-Un, B., Un, B., Akpolat, M. et al. Human Amnion Membrane-Derived Mesenchymal Stem Cells and Conditioned Medium Can Ameliorate X-Irradiation-Induced Testicular Injury by Reducing Endoplasmic Reticulum Stress and Apoptosis. Reprod. Sci. 29, 944–954 (2022). https://doi.org/10.1007/s43032-021-00753-6

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  • DOI: https://doi.org/10.1007/s43032-021-00753-6

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