Decreasing sperm quality in mice subjected to chronic cannabidiol exposure: New insights of cannabidiol-mediated male reproductive toxicity

Detalhes bibliográficos
Autor(a) principal: Carvalho, Renata K.
Data de Publicação: 2022
Outros Autores: Rocha, Thiago L., Fernandes, Fábio H., Gonçalves, Bruno B., Souza, Maingredy R., Araújo, Amanda A., Barbosa, Caio C., Silva, Daniela M., Campos, Hericles M., Tomazett, Mariana V., Ghedini, Paulo C., Guimarães, Francisco S., Andersen, Monica L., Santos, Fernanda C.A., Mazaro-Costa, Renata
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.cbi.2021.109743
http://hdl.handle.net/11449/231551
Resumo: Cannabidiol (CBD) is a natural cannabinoid present in the Cannabis sativa plant, widely prescribed as an anticonvulsant drug, especially for pediatric use. However, its effects on male reproduction are still little investigated. Therefore, the present study assessed the effects of CBD on the spermatogenesis and sperm quality. For this, twenty-one-day-old Swiss mice received CBD for 34 consecutive days by gavage at doses of either 15 or 30 mg/kg. Chronic exposure to CBD decreased the frequency of stages VII-VIII and XII of spermatogenesis and an increase in the frequency of stage IX were noted. Furthermore, the seminiferous epithelium height reduced at stage IX and increased at stage XII in both CBD-treated groups. There was a significant rise of sperm DNA damage, while no genotoxic effects were observed in leukocytes. The activities of superoxide dismutase and catalase decreased, while malondialdehyde levels increased in the sperm of mice treated with a higher dose of CBD. Mice exposed to 30 mg/kg of CBD showed a reduction in the mobile spermatozoa percentage and in curvilinear velocity, while straight line and average path velocity decreased in both treated groups. The number of acrosome-intact spermatozoa declined in the CBD 30 group, and the number of abnormal acrosomes raised in both CBD groups. On the other hand, the weight of reproductive organs, sperm count, and hormone levels were not affected by CBD treatment. These findings show that dysregulation of the endocannabinoid system by CBD can reduce sperm quality. The mechanisms responsible may be associated with disorders during spermatogenesis, especially during the final stages of nuclear remodelling and assembly of acrosome. However, changes in mitochondrial function, as well as the reduction on the antioxidant enzyme activities during epididymal transit, at least partly, may also be involved.
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spelling Decreasing sperm quality in mice subjected to chronic cannabidiol exposure: New insights of cannabidiol-mediated male reproductive toxicityAcrosome reactionDNA fragmentationEndocannabinoidsOxidative stressSperm motilitySpermatogenesisCannabidiol (CBD) is a natural cannabinoid present in the Cannabis sativa plant, widely prescribed as an anticonvulsant drug, especially for pediatric use. However, its effects on male reproduction are still little investigated. Therefore, the present study assessed the effects of CBD on the spermatogenesis and sperm quality. For this, twenty-one-day-old Swiss mice received CBD for 34 consecutive days by gavage at doses of either 15 or 30 mg/kg. Chronic exposure to CBD decreased the frequency of stages VII-VIII and XII of spermatogenesis and an increase in the frequency of stage IX were noted. Furthermore, the seminiferous epithelium height reduced at stage IX and increased at stage XII in both CBD-treated groups. There was a significant rise of sperm DNA damage, while no genotoxic effects were observed in leukocytes. The activities of superoxide dismutase and catalase decreased, while malondialdehyde levels increased in the sperm of mice treated with a higher dose of CBD. Mice exposed to 30 mg/kg of CBD showed a reduction in the mobile spermatozoa percentage and in curvilinear velocity, while straight line and average path velocity decreased in both treated groups. The number of acrosome-intact spermatozoa declined in the CBD 30 group, and the number of abnormal acrosomes raised in both CBD groups. On the other hand, the weight of reproductive organs, sperm count, and hormone levels were not affected by CBD treatment. These findings show that dysregulation of the endocannabinoid system by CBD can reduce sperm quality. The mechanisms responsible may be associated with disorders during spermatogenesis, especially during the final stages of nuclear remodelling and assembly of acrosome. However, changes in mitochondrial function, as well as the reduction on the antioxidant enzyme activities during epididymal transit, at least partly, may also be involved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de GoiásDepartment of Pharmacology Laboratory of Physiology and Pharmacology of Reproduction Federal University of GoiásLaboratory of Environmental Biotechnology and Ecotoxicology Institute of Tropical Pathology and Public Health Federal University of GoiásDepartment of Pathology Laboratory of Toxicogenomic and Nutrigenomic Medical School State University of São PauloDepartment of Genetics Laboratory of Mutagenesis Federal University of GoiásDepartment of Pharmacology Laboratory of Molecular and Biochemistry Pharmacology Federal University of GoiásLaboratory of Molecular Biology Federal University of GoiásDepartment of Pharmacology Ribeirão Preto Medical School University of São PauloDepartment of Psychobiology Federal University of São PauloDepartment of Histology Embryology and Cell Biology Laboratory of Microscopy Applied to Reproduction Federal University of GoiásUniversidade Federal de Goiás (UFG)Universidade de São Paulo (USP)Carvalho, Renata K.Rocha, Thiago L.Fernandes, Fábio H.Gonçalves, Bruno B.Souza, Maingredy R.Araújo, Amanda A.Barbosa, Caio C.Silva, Daniela M.Campos, Hericles M.Tomazett, Mariana V.Ghedini, Paulo C.Guimarães, Francisco S.Andersen, Monica L.Santos, Fernanda C.A.Mazaro-Costa, Renata2022-04-29T08:46:06Z2022-04-29T08:46:06Z2022-01-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.cbi.2021.109743Chemico-Biological Interactions, v. 351.1872-77860009-2797http://hdl.handle.net/11449/23155110.1016/j.cbi.2021.1097432-s2.0-85119036598Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengChemico-Biological Interactionsinfo:eu-repo/semantics/openAccess2022-04-29T08:46:06Zoai:repositorio.unesp.br:11449/231551Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462022-04-29T08:46:06Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Decreasing sperm quality in mice subjected to chronic cannabidiol exposure: New insights of cannabidiol-mediated male reproductive toxicity
title Decreasing sperm quality in mice subjected to chronic cannabidiol exposure: New insights of cannabidiol-mediated male reproductive toxicity
spellingShingle Decreasing sperm quality in mice subjected to chronic cannabidiol exposure: New insights of cannabidiol-mediated male reproductive toxicity
Carvalho, Renata K.
Acrosome reaction
DNA fragmentation
Endocannabinoids
Oxidative stress
Sperm motility
Spermatogenesis
title_short Decreasing sperm quality in mice subjected to chronic cannabidiol exposure: New insights of cannabidiol-mediated male reproductive toxicity
title_full Decreasing sperm quality in mice subjected to chronic cannabidiol exposure: New insights of cannabidiol-mediated male reproductive toxicity
title_fullStr Decreasing sperm quality in mice subjected to chronic cannabidiol exposure: New insights of cannabidiol-mediated male reproductive toxicity
title_full_unstemmed Decreasing sperm quality in mice subjected to chronic cannabidiol exposure: New insights of cannabidiol-mediated male reproductive toxicity
title_sort Decreasing sperm quality in mice subjected to chronic cannabidiol exposure: New insights of cannabidiol-mediated male reproductive toxicity
author Carvalho, Renata K.
author_facet Carvalho, Renata K.
Rocha, Thiago L.
Fernandes, Fábio H.
Gonçalves, Bruno B.
Souza, Maingredy R.
Araújo, Amanda A.
Barbosa, Caio C.
Silva, Daniela M.
Campos, Hericles M.
Tomazett, Mariana V.
Ghedini, Paulo C.
Guimarães, Francisco S.
Andersen, Monica L.
Santos, Fernanda C.A.
Mazaro-Costa, Renata
author_role author
author2 Rocha, Thiago L.
Fernandes, Fábio H.
Gonçalves, Bruno B.
Souza, Maingredy R.
Araújo, Amanda A.
Barbosa, Caio C.
Silva, Daniela M.
Campos, Hericles M.
Tomazett, Mariana V.
Ghedini, Paulo C.
Guimarães, Francisco S.
Andersen, Monica L.
Santos, Fernanda C.A.
Mazaro-Costa, Renata
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Federal de Goiás (UFG)
Universidade de São Paulo (USP)
dc.contributor.author.fl_str_mv Carvalho, Renata K.
Rocha, Thiago L.
Fernandes, Fábio H.
Gonçalves, Bruno B.
Souza, Maingredy R.
Araújo, Amanda A.
Barbosa, Caio C.
Silva, Daniela M.
Campos, Hericles M.
Tomazett, Mariana V.
Ghedini, Paulo C.
Guimarães, Francisco S.
Andersen, Monica L.
Santos, Fernanda C.A.
Mazaro-Costa, Renata
dc.subject.por.fl_str_mv Acrosome reaction
DNA fragmentation
Endocannabinoids
Oxidative stress
Sperm motility
Spermatogenesis
topic Acrosome reaction
DNA fragmentation
Endocannabinoids
Oxidative stress
Sperm motility
Spermatogenesis
description Cannabidiol (CBD) is a natural cannabinoid present in the Cannabis sativa plant, widely prescribed as an anticonvulsant drug, especially for pediatric use. However, its effects on male reproduction are still little investigated. Therefore, the present study assessed the effects of CBD on the spermatogenesis and sperm quality. For this, twenty-one-day-old Swiss mice received CBD for 34 consecutive days by gavage at doses of either 15 or 30 mg/kg. Chronic exposure to CBD decreased the frequency of stages VII-VIII and XII of spermatogenesis and an increase in the frequency of stage IX were noted. Furthermore, the seminiferous epithelium height reduced at stage IX and increased at stage XII in both CBD-treated groups. There was a significant rise of sperm DNA damage, while no genotoxic effects were observed in leukocytes. The activities of superoxide dismutase and catalase decreased, while malondialdehyde levels increased in the sperm of mice treated with a higher dose of CBD. Mice exposed to 30 mg/kg of CBD showed a reduction in the mobile spermatozoa percentage and in curvilinear velocity, while straight line and average path velocity decreased in both treated groups. The number of acrosome-intact spermatozoa declined in the CBD 30 group, and the number of abnormal acrosomes raised in both CBD groups. On the other hand, the weight of reproductive organs, sperm count, and hormone levels were not affected by CBD treatment. These findings show that dysregulation of the endocannabinoid system by CBD can reduce sperm quality. The mechanisms responsible may be associated with disorders during spermatogenesis, especially during the final stages of nuclear remodelling and assembly of acrosome. However, changes in mitochondrial function, as well as the reduction on the antioxidant enzyme activities during epididymal transit, at least partly, may also be involved.
publishDate 2022
dc.date.none.fl_str_mv 2022-04-29T08:46:06Z
2022-04-29T08:46:06Z
2022-01-05
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.cbi.2021.109743
Chemico-Biological Interactions, v. 351.
1872-7786
0009-2797
http://hdl.handle.net/11449/231551
10.1016/j.cbi.2021.109743
2-s2.0-85119036598
url http://dx.doi.org/10.1016/j.cbi.2021.109743
http://hdl.handle.net/11449/231551
identifier_str_mv Chemico-Biological Interactions, v. 351.
1872-7786
0009-2797
10.1016/j.cbi.2021.109743
2-s2.0-85119036598
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Chemico-Biological Interactions
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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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