Arsenic trioxide exposure impairs testicular morphology in adult male mice and consequent fetus viability
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1080/15287394.2017.1376405 http://hdl.handle.net/11449/179245 |
Resumo: | The acute promyelocytic leukemia (APL) is a rare disease, affecting 0.1/100,000 individuals globally. Despite significant advances in APL therapy, some patients still experience relapsed disease. Currently, arsenic trioxide (As2O3) was found to be effective in relapsed APL treatment and considered as standard treatment for these cases. However, it has been shown that exposure to As2O3 may exert adverse effects on the male reproductive system since this substance might also induce apoptosis of other important cell types including stem cells. Studies demonstrated that treatment with this metallic substance decreased plasma levels of testosterone and interfered with sperm parameters such as concentration, motility, and viability. In addition, As2O3 was found to produce significant damage to spermatocytes, which may be associated with testicular toxicity and consequent inhibition of spermatogenesis. The aim of this study was to determine subchronic treatment effects of As2O3 on sperm and testicular morphology, androgen receptor (AR) immunoreactivity in testes and epididymis, in addition to evaluation of fertility parameters in adult male mice. Thirty adult Swiss mice were divided into three experimental groups: control; received distilled water (vehicle) while treated received 0.3 or 3 mg/kg/day As2O3 subcutaneously, for 5 days per week, followed by 2 days of interruption, for 5 weeks. Results showed that As2O3 (1) decreased spermatozoa number, (2) produced seminiferous epithelium degeneration and exfoliation of germ cells tubule lumen (3) altered nucleus/cytoplasm proportion of Leydig cells and (4) reduced AR immunoreactivity in both Leydig and epithelial epididymal cells. Further, fetal viability tests demonstrated an increase in post-implantation loss in females that were mated with As2O3- treated males. Data indicate that As2O3 exposure altered the spermatogenic process and subsequently fetal viability. |
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Arsenic trioxide exposure impairs testicular morphology in adult male mice and consequent fetus viabilityAndrogen receptorArsenic trioxidePost-implantation lossSperm malformationToxicologyThe acute promyelocytic leukemia (APL) is a rare disease, affecting 0.1/100,000 individuals globally. Despite significant advances in APL therapy, some patients still experience relapsed disease. Currently, arsenic trioxide (As2O3) was found to be effective in relapsed APL treatment and considered as standard treatment for these cases. However, it has been shown that exposure to As2O3 may exert adverse effects on the male reproductive system since this substance might also induce apoptosis of other important cell types including stem cells. Studies demonstrated that treatment with this metallic substance decreased plasma levels of testosterone and interfered with sperm parameters such as concentration, motility, and viability. In addition, As2O3 was found to produce significant damage to spermatocytes, which may be associated with testicular toxicity and consequent inhibition of spermatogenesis. The aim of this study was to determine subchronic treatment effects of As2O3 on sperm and testicular morphology, androgen receptor (AR) immunoreactivity in testes and epididymis, in addition to evaluation of fertility parameters in adult male mice. Thirty adult Swiss mice were divided into three experimental groups: control; received distilled water (vehicle) while treated received 0.3 or 3 mg/kg/day As2O3 subcutaneously, for 5 days per week, followed by 2 days of interruption, for 5 weeks. Results showed that As2O3 (1) decreased spermatozoa number, (2) produced seminiferous epithelium degeneration and exfoliation of germ cells tubule lumen (3) altered nucleus/cytoplasm proportion of Leydig cells and (4) reduced AR immunoreactivity in both Leydig and epithelial epididymal cells. Further, fetal viability tests demonstrated an increase in post-implantation loss in females that were mated with As2O3- treated males. Data indicate that As2O3 exposure altered the spermatogenic process and subsequently fetal viability.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Structural and Functional Biology Institute of Biology University of Campinas (UNICAMP)Department of Morphology Institute of Biosciences Univ Estadual Paulista (UNESP)Department of Morphology Institute of Biosciences Univ Estadual Paulista (UNESP)FAPESP: FAPESP 2012/14342-8Universidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (Unesp)da Silva, Raquel FrenedosoBorges, Cibele dos Santos [UNESP]Lamas, Celina de AlmeidaCagnon, Valéria Helena AlvesKempinas, Wilma de Grava [UNESP]2018-12-11T17:34:21Z2018-12-11T17:34:21Z2017-09-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1166-1179application/pdfhttp://dx.doi.org/10.1080/15287394.2017.1376405Journal of Toxicology and Environmental Health - Part A: Current Issues, v. 80, n. 19-21, p. 1166-1179, 2017.1087-26201528-7394http://hdl.handle.net/11449/17924510.1080/15287394.2017.13764052-s2.0-850301810652-s2.0-85030181065.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Toxicology and Environmental Health - Part A: Current Issues0,8880,888info:eu-repo/semantics/openAccess2024-01-24T06:33:51Zoai:repositorio.unesp.br:11449/179245Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T23:51:49.707980Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Arsenic trioxide exposure impairs testicular morphology in adult male mice and consequent fetus viability |
title |
Arsenic trioxide exposure impairs testicular morphology in adult male mice and consequent fetus viability |
spellingShingle |
Arsenic trioxide exposure impairs testicular morphology in adult male mice and consequent fetus viability da Silva, Raquel Frenedoso Androgen receptor Arsenic trioxide Post-implantation loss Sperm malformation Toxicology |
title_short |
Arsenic trioxide exposure impairs testicular morphology in adult male mice and consequent fetus viability |
title_full |
Arsenic trioxide exposure impairs testicular morphology in adult male mice and consequent fetus viability |
title_fullStr |
Arsenic trioxide exposure impairs testicular morphology in adult male mice and consequent fetus viability |
title_full_unstemmed |
Arsenic trioxide exposure impairs testicular morphology in adult male mice and consequent fetus viability |
title_sort |
Arsenic trioxide exposure impairs testicular morphology in adult male mice and consequent fetus viability |
author |
da Silva, Raquel Frenedoso |
author_facet |
da Silva, Raquel Frenedoso Borges, Cibele dos Santos [UNESP] Lamas, Celina de Almeida Cagnon, Valéria Helena Alves Kempinas, Wilma de Grava [UNESP] |
author_role |
author |
author2 |
Borges, Cibele dos Santos [UNESP] Lamas, Celina de Almeida Cagnon, Valéria Helena Alves Kempinas, Wilma de Grava [UNESP] |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Campinas (UNICAMP) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
da Silva, Raquel Frenedoso Borges, Cibele dos Santos [UNESP] Lamas, Celina de Almeida Cagnon, Valéria Helena Alves Kempinas, Wilma de Grava [UNESP] |
dc.subject.por.fl_str_mv |
Androgen receptor Arsenic trioxide Post-implantation loss Sperm malformation Toxicology |
topic |
Androgen receptor Arsenic trioxide Post-implantation loss Sperm malformation Toxicology |
description |
The acute promyelocytic leukemia (APL) is a rare disease, affecting 0.1/100,000 individuals globally. Despite significant advances in APL therapy, some patients still experience relapsed disease. Currently, arsenic trioxide (As2O3) was found to be effective in relapsed APL treatment and considered as standard treatment for these cases. However, it has been shown that exposure to As2O3 may exert adverse effects on the male reproductive system since this substance might also induce apoptosis of other important cell types including stem cells. Studies demonstrated that treatment with this metallic substance decreased plasma levels of testosterone and interfered with sperm parameters such as concentration, motility, and viability. In addition, As2O3 was found to produce significant damage to spermatocytes, which may be associated with testicular toxicity and consequent inhibition of spermatogenesis. The aim of this study was to determine subchronic treatment effects of As2O3 on sperm and testicular morphology, androgen receptor (AR) immunoreactivity in testes and epididymis, in addition to evaluation of fertility parameters in adult male mice. Thirty adult Swiss mice were divided into three experimental groups: control; received distilled water (vehicle) while treated received 0.3 or 3 mg/kg/day As2O3 subcutaneously, for 5 days per week, followed by 2 days of interruption, for 5 weeks. Results showed that As2O3 (1) decreased spermatozoa number, (2) produced seminiferous epithelium degeneration and exfoliation of germ cells tubule lumen (3) altered nucleus/cytoplasm proportion of Leydig cells and (4) reduced AR immunoreactivity in both Leydig and epithelial epididymal cells. Further, fetal viability tests demonstrated an increase in post-implantation loss in females that were mated with As2O3- treated males. Data indicate that As2O3 exposure altered the spermatogenic process and subsequently fetal viability. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-09-29 2018-12-11T17:34:21Z 2018-12-11T17:34:21Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1080/15287394.2017.1376405 Journal of Toxicology and Environmental Health - Part A: Current Issues, v. 80, n. 19-21, p. 1166-1179, 2017. 1087-2620 1528-7394 http://hdl.handle.net/11449/179245 10.1080/15287394.2017.1376405 2-s2.0-85030181065 2-s2.0-85030181065.pdf |
url |
http://dx.doi.org/10.1080/15287394.2017.1376405 http://hdl.handle.net/11449/179245 |
identifier_str_mv |
Journal of Toxicology and Environmental Health - Part A: Current Issues, v. 80, n. 19-21, p. 1166-1179, 2017. 1087-2620 1528-7394 10.1080/15287394.2017.1376405 2-s2.0-85030181065 2-s2.0-85030181065.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Toxicology and Environmental Health - Part A: Current Issues 0,888 0,888 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1166-1179 application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808129559366729728 |