Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0066091 http://hdl.handle.net/11449/75643 |
Resumo: | Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day) or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin-norepinephrine reuptake inhibitors, especially considering the lower reproductive efficiency of humans compared to males of other species. © 2013 Borges et al. |
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Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutraminenoradrenalinsibutramineadrenergic stimulationanimal cellanimal experimentanimal modelanimal tissuecatecholamine depletioncell structureconcentration responsecontrolled studyepididymisex vivo studyhormone determinationin vivo studylong term exposuremalemale infertilitynonhumannoradrenalin blood levelprostate sizeratreproductive toxicityspermatozoon capacitationspermatozoon motilitytestis functionSperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day) or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin-norepinephrine reuptake inhibitors, especially considering the lower reproductive efficiency of humans compared to males of other species. © 2013 Borges et al.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Morphology Institute of Biosciences Universidade Estadual Paulista (UNESP), Botucatu, São PauloDepartment of Pharmacology Institute of Biosciences Universidade Estadual Paulista (UNESP), Botucatu, São PauloDepartment of Morphology Institute of Biosciences Universidade Estadual Paulista (UNESP), Botucatu, São PauloDepartment of Pharmacology Institute of Biosciences Universidade Estadual Paulista (UNESP), Botucatu, São PauloFAPESP: 10/13948-4FAPESP: 11/11840-4CNPq: 304958/2009-3Universidade Estadual Paulista (Unesp)Borges, Cibele S. [UNESP]Missassi, Gabriela [UNESP]Pacini, Enio S. A. [UNESP]Kiguti, Luiz Ricardo A. [UNESP]Sanabria, Marciana [UNESP]Silva, Raquel F. [UNESP]Banzato, Thais P. [UNESP]Perobelli, Juliana E. [UNESP]Pupo, André S. [UNESP]Kempinas, Wilma G. [UNESP]2014-05-27T11:29:40Z2014-05-27T11:29:40Z2013-06-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1371/journal.pone.0066091PLoS ONE, v. 8, n. 6, 2013.1932-6203http://hdl.handle.net/11449/7564310.1371/journal.pone.0066091WOS:0003203224000802-s2.0-848789547662-s2.0-84878954766.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPLOS ONE2.7661,164info:eu-repo/semantics/openAccess2023-12-29T06:19:16Zoai:repositorio.unesp.br:11449/75643Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:35:52.077319Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine |
title |
Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine |
spellingShingle |
Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine Borges, Cibele S. [UNESP] noradrenalin sibutramine adrenergic stimulation animal cell animal experiment animal model animal tissue catecholamine depletion cell structure concentration response controlled study epididymis ex vivo study hormone determination in vivo study long term exposure male male infertility nonhuman noradrenalin blood level prostate size rat reproductive toxicity spermatozoon capacitation spermatozoon motility testis function |
title_short |
Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine |
title_full |
Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine |
title_fullStr |
Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine |
title_full_unstemmed |
Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine |
title_sort |
Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine |
author |
Borges, Cibele S. [UNESP] |
author_facet |
Borges, Cibele S. [UNESP] Missassi, Gabriela [UNESP] Pacini, Enio S. A. [UNESP] Kiguti, Luiz Ricardo A. [UNESP] Sanabria, Marciana [UNESP] Silva, Raquel F. [UNESP] Banzato, Thais P. [UNESP] Perobelli, Juliana E. [UNESP] Pupo, André S. [UNESP] Kempinas, Wilma G. [UNESP] |
author_role |
author |
author2 |
Missassi, Gabriela [UNESP] Pacini, Enio S. A. [UNESP] Kiguti, Luiz Ricardo A. [UNESP] Sanabria, Marciana [UNESP] Silva, Raquel F. [UNESP] Banzato, Thais P. [UNESP] Perobelli, Juliana E. [UNESP] Pupo, André S. [UNESP] Kempinas, Wilma G. [UNESP] |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Borges, Cibele S. [UNESP] Missassi, Gabriela [UNESP] Pacini, Enio S. A. [UNESP] Kiguti, Luiz Ricardo A. [UNESP] Sanabria, Marciana [UNESP] Silva, Raquel F. [UNESP] Banzato, Thais P. [UNESP] Perobelli, Juliana E. [UNESP] Pupo, André S. [UNESP] Kempinas, Wilma G. [UNESP] |
dc.subject.por.fl_str_mv |
noradrenalin sibutramine adrenergic stimulation animal cell animal experiment animal model animal tissue catecholamine depletion cell structure concentration response controlled study epididymis ex vivo study hormone determination in vivo study long term exposure male male infertility nonhuman noradrenalin blood level prostate size rat reproductive toxicity spermatozoon capacitation spermatozoon motility testis function |
topic |
noradrenalin sibutramine adrenergic stimulation animal cell animal experiment animal model animal tissue catecholamine depletion cell structure concentration response controlled study epididymis ex vivo study hormone determination in vivo study long term exposure male male infertility nonhuman noradrenalin blood level prostate size rat reproductive toxicity spermatozoon capacitation spermatozoon motility testis function |
description |
Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day) or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin-norepinephrine reuptake inhibitors, especially considering the lower reproductive efficiency of humans compared to males of other species. © 2013 Borges et al. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-06-12 2014-05-27T11:29:40Z 2014-05-27T11:29:40Z |
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/10.1371/journal.pone.0066091 PLoS ONE, v. 8, n. 6, 2013. 1932-6203 http://hdl.handle.net/11449/75643 10.1371/journal.pone.0066091 WOS:000320322400080 2-s2.0-84878954766 2-s2.0-84878954766.pdf |
url |
http://dx.doi.org/10.1371/journal.pone.0066091 http://hdl.handle.net/11449/75643 |
identifier_str_mv |
PLoS ONE, v. 8, n. 6, 2013. 1932-6203 10.1371/journal.pone.0066091 WOS:000320322400080 2-s2.0-84878954766 2-s2.0-84878954766.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLOS ONE 2.766 1,164 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
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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1808129340053913600 |