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Treosulfan induces distinctive gonadal toxicity compared with busulfan

Treosulfan (L-treitol-1,4-bis-methanesulfonate) has been increasingly incorporated as a main conditioning protocol for hematopoietic stem cell transplantation in pediatric malignant and non-malignant diseases. Treosulfan presents lower toxicity profile than other conventional alkylating agents conta...

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Autores principales: Levi, Mattan, Stemmer, Salomon M., Stein, Jerry, Shalgi, Ruth, Ben-Aharon, Irit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922399/
https://www.ncbi.nlm.nih.gov/pubmed/29721205
http://dx.doi.org/10.18632/oncotarget.25029
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author Levi, Mattan
Stemmer, Salomon M.
Stein, Jerry
Shalgi, Ruth
Ben-Aharon, Irit
author_facet Levi, Mattan
Stemmer, Salomon M.
Stein, Jerry
Shalgi, Ruth
Ben-Aharon, Irit
author_sort Levi, Mattan
collection PubMed
description Treosulfan (L-treitol-1,4-bis-methanesulfonate) has been increasingly incorporated as a main conditioning protocol for hematopoietic stem cell transplantation in pediatric malignant and non-malignant diseases. Treosulfan presents lower toxicity profile than other conventional alkylating agents containing myeloablative and immunosuppressive traits such as busulfan. Yet, whereas busulfan is considered highly gonadotoxic, the gonadal toxicity profile of treosulfan remains to be elucidated. To study the gonadotoxicity of treosulfan, pubertal and prepubertal male and female mice were injected with treosulfan or busulfan and sacrificed one week, one month or six months later. Testicular function was assessed by measurements of sperm properties, testes and epididymides weights as well as markers for testicular reserve, proliferation and apoptosis. Ovarian function was assessed by measurements of ovary weight and markers for ovarian reserve, proliferation and apoptosis. Treosulfan testicular toxicity was milder than that of busulfan toxicity; possibly by sparing the stem spermatogonia in the testicular sanctuary. By contrast, ovarian toxicity of both treosulfan and busulfan was severe and permanent and displayed irreversible reduction of reserve primordial follicles in the ovaries. Our data indicate that treosulfan exerts a different gonadal toxicity profile from busulfan, manifested by mild testicular toxicity and severe ovarian toxicity.
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spelling pubmed-59223992018-05-02 Treosulfan induces distinctive gonadal toxicity compared with busulfan Levi, Mattan Stemmer, Salomon M. Stein, Jerry Shalgi, Ruth Ben-Aharon, Irit Oncotarget Research Paper Treosulfan (L-treitol-1,4-bis-methanesulfonate) has been increasingly incorporated as a main conditioning protocol for hematopoietic stem cell transplantation in pediatric malignant and non-malignant diseases. Treosulfan presents lower toxicity profile than other conventional alkylating agents containing myeloablative and immunosuppressive traits such as busulfan. Yet, whereas busulfan is considered highly gonadotoxic, the gonadal toxicity profile of treosulfan remains to be elucidated. To study the gonadotoxicity of treosulfan, pubertal and prepubertal male and female mice were injected with treosulfan or busulfan and sacrificed one week, one month or six months later. Testicular function was assessed by measurements of sperm properties, testes and epididymides weights as well as markers for testicular reserve, proliferation and apoptosis. Ovarian function was assessed by measurements of ovary weight and markers for ovarian reserve, proliferation and apoptosis. Treosulfan testicular toxicity was milder than that of busulfan toxicity; possibly by sparing the stem spermatogonia in the testicular sanctuary. By contrast, ovarian toxicity of both treosulfan and busulfan was severe and permanent and displayed irreversible reduction of reserve primordial follicles in the ovaries. Our data indicate that treosulfan exerts a different gonadal toxicity profile from busulfan, manifested by mild testicular toxicity and severe ovarian toxicity. Impact Journals LLC 2018-04-10 /pmc/articles/PMC5922399/ /pubmed/29721205 http://dx.doi.org/10.18632/oncotarget.25029 Text en Copyright: © 2018 Levi et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Levi, Mattan
Stemmer, Salomon M.
Stein, Jerry
Shalgi, Ruth
Ben-Aharon, Irit
Treosulfan induces distinctive gonadal toxicity compared with busulfan
title Treosulfan induces distinctive gonadal toxicity compared with busulfan
title_full Treosulfan induces distinctive gonadal toxicity compared with busulfan
title_fullStr Treosulfan induces distinctive gonadal toxicity compared with busulfan
title_full_unstemmed Treosulfan induces distinctive gonadal toxicity compared with busulfan
title_short Treosulfan induces distinctive gonadal toxicity compared with busulfan
title_sort treosulfan induces distinctive gonadal toxicity compared with busulfan
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922399/
https://www.ncbi.nlm.nih.gov/pubmed/29721205
http://dx.doi.org/10.18632/oncotarget.25029
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