Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty

Detalhes bibliográficos
Autor(a) principal: Barros, Jorge W.F.
Data de Publicação: 2020
Outros Autores: Tonon, Karolina S. [UNESP], Borges, Cibele S. [UNESP], Silva, Patrícia V. [UNESP], Lozano, Ana F.Q., Pacheco, Tainá L., Anselmo-Franci, Janete A., Kempinas, Wilma G. [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.crtox.2020.11.002
http://hdl.handle.net/11449/233123
Resumo: Statins are a class of drugs that act lowering lipid levels by inhibiting cholesterol biosynthesis. Additionally, statins can act by “pleiotropic effects”, related to the inhibition of synthesis of the other mevalonate pathway products. Rosuvastatin is a third-generation statin and has shown better results in reducing cholesterol concentrations when compared to other statins. Recent studies suggest that rosuvastatin may act as an endocrine disruptor that potentially damages the hormonal axis and, consequently reproductive development and function of male rats. However, the effects of rosuvastatin exposure on rat female reproductive parameters remain unknown. In this study female rats were exposed to rosuvastatin at the doses of 0 (control), 3, or 10 mg/Kg.bw−1/day from pre-puberty to adulthood. No alterations in the female reproductive parameters were observed at a dose of 3 mg/Kg.bw−1. However, females exposed to 10 mg/Kg.bw−1 exhibited shorter estrous cycles, altered copulatory behavior, decreased serum prolactin level, and alterations in the liver, pituitary and placental weights, parameters to some extent influenced by the reproductive hormonal axis signaling pathway. On the other hand, pubertal onset, reproductive hormone levels, fertility, and histological parameters of the ovary, uterus, and placenta were unaltered by exposure to both doses of this statin. Thus, rosuvastatin exposure, at the higher dose, altered the reproductive function of female rats, probably due to the pleiotropic effects of this statin. Additional studies on the effects of this statin on female reproductive function and development are encouraged to better characterize its mode of action.
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spelling Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-pubertyPleiotropic effectsRat female reproductionRosuvastatinStatinStatins are a class of drugs that act lowering lipid levels by inhibiting cholesterol biosynthesis. Additionally, statins can act by “pleiotropic effects”, related to the inhibition of synthesis of the other mevalonate pathway products. Rosuvastatin is a third-generation statin and has shown better results in reducing cholesterol concentrations when compared to other statins. Recent studies suggest that rosuvastatin may act as an endocrine disruptor that potentially damages the hormonal axis and, consequently reproductive development and function of male rats. However, the effects of rosuvastatin exposure on rat female reproductive parameters remain unknown. In this study female rats were exposed to rosuvastatin at the doses of 0 (control), 3, or 10 mg/Kg.bw−1/day from pre-puberty to adulthood. No alterations in the female reproductive parameters were observed at a dose of 3 mg/Kg.bw−1. However, females exposed to 10 mg/Kg.bw−1 exhibited shorter estrous cycles, altered copulatory behavior, decreased serum prolactin level, and alterations in the liver, pituitary and placental weights, parameters to some extent influenced by the reproductive hormonal axis signaling pathway. On the other hand, pubertal onset, reproductive hormone levels, fertility, and histological parameters of the ovary, uterus, and placenta were unaltered by exposure to both doses of this statin. Thus, rosuvastatin exposure, at the higher dose, altered the reproductive function of female rats, probably due to the pleiotropic effects of this statin. Additional studies on the effects of this statin on female reproductive function and development are encouraged to better characterize its mode of action.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Estadual PaulistaGraduate Program in Cell and Structural Biology Institute of Biology State University of Campinas (UNICAMP)Department of Structural and Functional Biology São Paulo State University (Unesp) Institute of BiosciencesDepartment of Morphology Stomatology and Physiology Dental School of Ribeirão Preto University of São Paulo (USP)Department of Structural and Functional Biology São Paulo State University (Unesp) Institute of BiosciencesUniversidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (UNESP)Universidade de São Paulo (USP)Barros, Jorge W.F.Tonon, Karolina S. [UNESP]Borges, Cibele S. [UNESP]Silva, Patrícia V. [UNESP]Lozano, Ana F.Q.Pacheco, Tainá L.Anselmo-Franci, Janete A.Kempinas, Wilma G. [UNESP]2022-05-01T04:26:34Z2022-05-01T04:26:34Z2020-06-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article149-160http://dx.doi.org/10.1016/j.crtox.2020.11.002Current Research in Toxicology, v. 1, p. 149-160.2666-027Xhttp://hdl.handle.net/11449/23312310.1016/j.crtox.2020.11.0022-s2.0-85105163163Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengCurrent Research in Toxicologyinfo:eu-repo/semantics/openAccess2022-05-01T04:26:34Zoai:repositorio.unesp.br:11449/233123Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T19:53:47.842949Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty
title Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty
spellingShingle Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty
Barros, Jorge W.F.
Pleiotropic effects
Rat female reproduction
Rosuvastatin
Statin
title_short Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty
title_full Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty
title_fullStr Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty
title_full_unstemmed Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty
title_sort Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty
author Barros, Jorge W.F.
author_facet Barros, Jorge W.F.
Tonon, Karolina S. [UNESP]
Borges, Cibele S. [UNESP]
Silva, Patrícia V. [UNESP]
Lozano, Ana F.Q.
Pacheco, Tainá L.
Anselmo-Franci, Janete A.
Kempinas, Wilma G. [UNESP]
author_role author
author2 Tonon, Karolina S. [UNESP]
Borges, Cibele S. [UNESP]
Silva, Patrícia V. [UNESP]
Lozano, Ana F.Q.
Pacheco, Tainá L.
Anselmo-Franci, Janete A.
Kempinas, Wilma G. [UNESP]
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual de Campinas (UNICAMP)
Universidade Estadual Paulista (UNESP)
Universidade de São Paulo (USP)
dc.contributor.author.fl_str_mv Barros, Jorge W.F.
Tonon, Karolina S. [UNESP]
Borges, Cibele S. [UNESP]
Silva, Patrícia V. [UNESP]
Lozano, Ana F.Q.
Pacheco, Tainá L.
Anselmo-Franci, Janete A.
Kempinas, Wilma G. [UNESP]
dc.subject.por.fl_str_mv Pleiotropic effects
Rat female reproduction
Rosuvastatin
Statin
topic Pleiotropic effects
Rat female reproduction
Rosuvastatin
Statin
description Statins are a class of drugs that act lowering lipid levels by inhibiting cholesterol biosynthesis. Additionally, statins can act by “pleiotropic effects”, related to the inhibition of synthesis of the other mevalonate pathway products. Rosuvastatin is a third-generation statin and has shown better results in reducing cholesterol concentrations when compared to other statins. Recent studies suggest that rosuvastatin may act as an endocrine disruptor that potentially damages the hormonal axis and, consequently reproductive development and function of male rats. However, the effects of rosuvastatin exposure on rat female reproductive parameters remain unknown. In this study female rats were exposed to rosuvastatin at the doses of 0 (control), 3, or 10 mg/Kg.bw−1/day from pre-puberty to adulthood. No alterations in the female reproductive parameters were observed at a dose of 3 mg/Kg.bw−1. However, females exposed to 10 mg/Kg.bw−1 exhibited shorter estrous cycles, altered copulatory behavior, decreased serum prolactin level, and alterations in the liver, pituitary and placental weights, parameters to some extent influenced by the reproductive hormonal axis signaling pathway. On the other hand, pubertal onset, reproductive hormone levels, fertility, and histological parameters of the ovary, uterus, and placenta were unaltered by exposure to both doses of this statin. Thus, rosuvastatin exposure, at the higher dose, altered the reproductive function of female rats, probably due to the pleiotropic effects of this statin. Additional studies on the effects of this statin on female reproductive function and development are encouraged to better characterize its mode of action.
publishDate 2020
dc.date.none.fl_str_mv 2020-06-10
2022-05-01T04:26:34Z
2022-05-01T04:26:34Z
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/10.1016/j.crtox.2020.11.002
Current Research in Toxicology, v. 1, p. 149-160.
2666-027X
http://hdl.handle.net/11449/233123
10.1016/j.crtox.2020.11.002
2-s2.0-85105163163
url http://dx.doi.org/10.1016/j.crtox.2020.11.002
http://hdl.handle.net/11449/233123
identifier_str_mv Current Research in Toxicology, v. 1, p. 149-160.
2666-027X
10.1016/j.crtox.2020.11.002
2-s2.0-85105163163
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Current Research in Toxicology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 149-160
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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