Anabolic Steroids-Driven Regulation of Porcine Ovarian Putative Stem Cells Favors the Onset of Their Neoplastic Transformation

Nandrolone (Ndn) and boldenone (Bdn), the synthetic testosterone analogues with strong anabolic effects, despite being recognized as potentially carcinogenic compounds, are commonly abused by athletes and bodybuilders, which includes women, worldwide. This study tested the hypothesis that different...

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Autores principales: Gabriela Gorczyca, Kamil Wartalski, Jerzy Wiater, Marcin Samiec, Zbigniew Tabarowski, Małgorzata Duda
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/a57a5b8e2c6845b1bf8dbf9c777e5458
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spelling oai:doaj.org-article:a57a5b8e2c6845b1bf8dbf9c777e54582021-11-11T17:14:45ZAnabolic Steroids-Driven Regulation of Porcine Ovarian Putative Stem Cells Favors the Onset of Their Neoplastic Transformation10.3390/ijms2221118001422-00671661-6596https://doaj.org/article/a57a5b8e2c6845b1bf8dbf9c777e54582021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11800https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Nandrolone (Ndn) and boldenone (Bdn), the synthetic testosterone analogues with strong anabolic effects, despite being recognized as potentially carcinogenic compounds, are commonly abused by athletes and bodybuilders, which includes women, worldwide. This study tested the hypothesis that different doses of Ndn and Bdn can initiate neoplastic transformation of porcine ovarian putative stem cells (poPSCs). Immunomagnetically isolated poPSCs were expanded ex vivo in the presence of Ndn or Bdn, for 7 and 14 days. Results show that pharmacological doses of both Ndn and Bdn, already after 7 days of poPSCs culture, caused a significant increase of selected, stemness-related markers of cancer cells: CD44 and CD133. Notably, Ndn also negatively affected poPSCs growth not only by suppressing their proliferation and mitochondrial respiration but also by inducing apoptosis. This observation shows, for the first time, that chronic exposure to Ndn or Bdn represents a precondition that might enhance risk of poPSCs neoplastic transformation. These studies carried out to accomplish detailed molecular characterization of the ex vivo expanded poPSCs and their potentially cancerous derivatives (PCDs) might be helpful to determine their suitability as nuclear donor cells (NDCs) for further investigations focused on cloning by somatic cell nuclear transfer (SCNT). Such investigations might also be indispensable to estimate the capabilities of nuclear genomes inherited from poPSCs and their PCDs to be epigenetically reprogrammed (dedifferentiated) in cloned pig embryos generated by SCNT. This might open up new possibilities for biomedical research aimed at more comprehensively recognizing genetic and epigenetic mechanisms underlying not only tumorigenesis but also reversal/retardation of pro-tumorigenic intracellular events.Gabriela GorczycaKamil WartalskiJerzy WiaterMarcin SamiecZbigniew TabarowskiMałgorzata DudaMDPI AGarticlepigovaryputative stem cellsnandroloneboldenoneneoplastic transformationBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11800, p 11800 (2021)
institution DOAJ
collection DOAJ
language EN
topic pig
ovary
putative stem cells
nandrolone
boldenone
neoplastic transformation
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle pig
ovary
putative stem cells
nandrolone
boldenone
neoplastic transformation
Biology (General)
QH301-705.5
Chemistry
QD1-999
Gabriela Gorczyca
Kamil Wartalski
Jerzy Wiater
Marcin Samiec
Zbigniew Tabarowski
Małgorzata Duda
Anabolic Steroids-Driven Regulation of Porcine Ovarian Putative Stem Cells Favors the Onset of Their Neoplastic Transformation
description Nandrolone (Ndn) and boldenone (Bdn), the synthetic testosterone analogues with strong anabolic effects, despite being recognized as potentially carcinogenic compounds, are commonly abused by athletes and bodybuilders, which includes women, worldwide. This study tested the hypothesis that different doses of Ndn and Bdn can initiate neoplastic transformation of porcine ovarian putative stem cells (poPSCs). Immunomagnetically isolated poPSCs were expanded ex vivo in the presence of Ndn or Bdn, for 7 and 14 days. Results show that pharmacological doses of both Ndn and Bdn, already after 7 days of poPSCs culture, caused a significant increase of selected, stemness-related markers of cancer cells: CD44 and CD133. Notably, Ndn also negatively affected poPSCs growth not only by suppressing their proliferation and mitochondrial respiration but also by inducing apoptosis. This observation shows, for the first time, that chronic exposure to Ndn or Bdn represents a precondition that might enhance risk of poPSCs neoplastic transformation. These studies carried out to accomplish detailed molecular characterization of the ex vivo expanded poPSCs and their potentially cancerous derivatives (PCDs) might be helpful to determine their suitability as nuclear donor cells (NDCs) for further investigations focused on cloning by somatic cell nuclear transfer (SCNT). Such investigations might also be indispensable to estimate the capabilities of nuclear genomes inherited from poPSCs and their PCDs to be epigenetically reprogrammed (dedifferentiated) in cloned pig embryos generated by SCNT. This might open up new possibilities for biomedical research aimed at more comprehensively recognizing genetic and epigenetic mechanisms underlying not only tumorigenesis but also reversal/retardation of pro-tumorigenic intracellular events.
format article
author Gabriela Gorczyca
Kamil Wartalski
Jerzy Wiater
Marcin Samiec
Zbigniew Tabarowski
Małgorzata Duda
author_facet Gabriela Gorczyca
Kamil Wartalski
Jerzy Wiater
Marcin Samiec
Zbigniew Tabarowski
Małgorzata Duda
author_sort Gabriela Gorczyca
title Anabolic Steroids-Driven Regulation of Porcine Ovarian Putative Stem Cells Favors the Onset of Their Neoplastic Transformation
title_short Anabolic Steroids-Driven Regulation of Porcine Ovarian Putative Stem Cells Favors the Onset of Their Neoplastic Transformation
title_full Anabolic Steroids-Driven Regulation of Porcine Ovarian Putative Stem Cells Favors the Onset of Their Neoplastic Transformation
title_fullStr Anabolic Steroids-Driven Regulation of Porcine Ovarian Putative Stem Cells Favors the Onset of Their Neoplastic Transformation
title_full_unstemmed Anabolic Steroids-Driven Regulation of Porcine Ovarian Putative Stem Cells Favors the Onset of Their Neoplastic Transformation
title_sort anabolic steroids-driven regulation of porcine ovarian putative stem cells favors the onset of their neoplastic transformation
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/a57a5b8e2c6845b1bf8dbf9c777e5458
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