Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , |
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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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 |
|
_version_ |
1808129137163894784 |