Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the sperm

Autores
Gonzalez, Betina; Gambini Pantoja, Camilo; Vitullo, Alfredo Daniel; Bisagno, Veronica; Gonzalez, Candela Rocio
Año de publicación
2018
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Cocaine intake is associated with testicular toxicity and significantreproductive function impairment. There is accumulating evidencethat cocaine administration can trigger nongenetic inheritancethrough the male germ line affecting development and behavior ofthe offspring. The influence of environmental factors on the epigenomeof male germ cells appears to be most impactful if it happensduring a developmental phase when these cells are epigeneticallyreprogrammed. In the present study, we measured epigenetic marksin isolated germ cells of adult mice treated with cocaine (10 mg/kg) or vehicle, in an intermittent binge protocol (3 i.p. injections, 1h apart, one day on/off for 13 days). We found that chronic cocaineintake disrupts male germ cell epigenetic homeostasis, increasingglobal methylated citocine (5-mC) levels in DNA from germ cells andcauda epididymal sperm (germ cells: vehicle 13.15 ± 0.99 vs cocaine20.113 ± 2.28; sperm: vehicle 15.81 ± 1.08 vs cocaine 21.35± 1.52). Cocaine also increased acetylated histone 4 (H4ac) proteinlevels and decreased class I deacetylases HDAC1/2 mRNA andprotein expression (p<0.05). The mRNA expression levels of classIIa and IIb HDACs were also altered (p<0.05). Immunolocalizationstudies showed that HDAC1/2 were mainly expressed in primaryspermatocytes and H4ac was immunolocalized in late meiotic stagesin vehicle mice while it was detected in primary spermatocytesand in successive stages until round spermatid in cocaine-treatedmice. We observed altered mRNA expression of DNA methylationmarkers in isolated germ cells showing decreased levels of Dnmt3band Tet1 gene expression after cocaine treatment (p<0.05). TET1was mainly immunolocalized in primary spermatocytes in vehicleand cocaine-treated mice. The results presented here broaden thebasic knowledge of the impact of addictive stimulants on testicularpathophysiology, fertility and male reproductive health and implythat altered epigenetic homeostasis by cocaine may have potentialconsequences on future generations.
Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Gambini Pantoja, Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Vitullo, Alfredo Daniel. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bisagno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Gonzalez, Candela Rocio. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVI Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Asociación Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Asociación Argentina de Fisiología
Asociación Argentina de Virología
Asociación Argentina de Nanomedicinas
Materia
COCAINE
MALE GERM CELLS
HISTONE ACETYLATION
DNA METHYLATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/199139
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/199139
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the spermGonzalez, BetinaGambini Pantoja, CamiloVitullo, Alfredo DanielBisagno, VeronicaGonzalez, Candela RocioCOCAINEMALE GERM CELLSHISTONE ACETYLATIONDNA METHYLATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Cocaine intake is associated with testicular toxicity and significantreproductive function impairment. There is accumulating evidencethat cocaine administration can trigger nongenetic inheritancethrough the male germ line affecting development and behavior ofthe offspring. The influence of environmental factors on the epigenomeof male germ cells appears to be most impactful if it happensduring a developmental phase when these cells are epigeneticallyreprogrammed. In the present study, we measured epigenetic marksin isolated germ cells of adult mice treated with cocaine (10 mg/kg) or vehicle, in an intermittent binge protocol (3 i.p. injections, 1h apart, one day on/off for 13 days). We found that chronic cocaineintake disrupts male germ cell epigenetic homeostasis, increasingglobal methylated citocine (5-mC) levels in DNA from germ cells andcauda epididymal sperm (germ cells: vehicle 13.15 ± 0.99 vs cocaine20.113 ± 2.28; sperm: vehicle 15.81 ± 1.08 vs cocaine 21.35± 1.52). Cocaine also increased acetylated histone 4 (H4ac) proteinlevels and decreased class I deacetylases HDAC1/2 mRNA andprotein expression (p<0.05). The mRNA expression levels of classIIa and IIb HDACs were also altered (p<0.05). Immunolocalizationstudies showed that HDAC1/2 were mainly expressed in primaryspermatocytes and H4ac was immunolocalized in late meiotic stagesin vehicle mice while it was detected in primary spermatocytesand in successive stages until round spermatid in cocaine-treatedmice. We observed altered mRNA expression of DNA methylationmarkers in isolated germ cells showing decreased levels of Dnmt3band Tet1 gene expression after cocaine treatment (p<0.05). TET1was mainly immunolocalized in primary spermatocytes in vehicleand cocaine-treated mice. The results presented here broaden thebasic knowledge of the impact of addictive stimulants on testicularpathophysiology, fertility and male reproductive health and implythat altered epigenetic homeostasis by cocaine may have potentialconsequences on future generations.Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Gambini Pantoja, Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Vitullo, Alfredo Daniel. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bisagno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Gonzalez, Candela Rocio. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaLXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVI Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Asociación Argentina de FisiologíaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de FisiologíaAsociación Argentina de VirologíaAsociación Argentina de NanomedicinasFundacion Revista Medicina2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/199139Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the sperm; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVI Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Asociación Argentina de Fisiología; Mar del Plata; Argentina; 2018; 105-1051669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/reunion-anualNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:34:13Zoai:ri.conicet.gov.ar:11336/199139instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:34:14.133CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the sperm
title Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the sperm
spellingShingle Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the sperm
Gonzalez, Betina
COCAINE
MALE GERM CELLS
HISTONE ACETYLATION
DNA METHYLATION
title_short Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the sperm
title_full Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the sperm
title_fullStr Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the sperm
title_full_unstemmed Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the sperm
title_sort Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the sperm
dc.creator.none.fl_str_mv Gonzalez, Betina
Gambini Pantoja, Camilo
Vitullo, Alfredo Daniel
Bisagno, Veronica
Gonzalez, Candela Rocio
author Gonzalez, Betina
author_facet Gonzalez, Betina
Gambini Pantoja, Camilo
Vitullo, Alfredo Daniel
Bisagno, Veronica
Gonzalez, Candela Rocio
author_role author
author2 Gambini Pantoja, Camilo
Vitullo, Alfredo Daniel
Bisagno, Veronica
Gonzalez, Candela Rocio
author2_role author
author
author
author
dc.subject.none.fl_str_mv COCAINE
MALE GERM CELLS
HISTONE ACETYLATION
DNA METHYLATION
topic COCAINE
MALE GERM CELLS
HISTONE ACETYLATION
DNA METHYLATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cocaine intake is associated with testicular toxicity and significantreproductive function impairment. There is accumulating evidencethat cocaine administration can trigger nongenetic inheritancethrough the male germ line affecting development and behavior ofthe offspring. The influence of environmental factors on the epigenomeof male germ cells appears to be most impactful if it happensduring a developmental phase when these cells are epigeneticallyreprogrammed. In the present study, we measured epigenetic marksin isolated germ cells of adult mice treated with cocaine (10 mg/kg) or vehicle, in an intermittent binge protocol (3 i.p. injections, 1h apart, one day on/off for 13 days). We found that chronic cocaineintake disrupts male germ cell epigenetic homeostasis, increasingglobal methylated citocine (5-mC) levels in DNA from germ cells andcauda epididymal sperm (germ cells: vehicle 13.15 ± 0.99 vs cocaine20.113 ± 2.28; sperm: vehicle 15.81 ± 1.08 vs cocaine 21.35± 1.52). Cocaine also increased acetylated histone 4 (H4ac) proteinlevels and decreased class I deacetylases HDAC1/2 mRNA andprotein expression (p<0.05). The mRNA expression levels of classIIa and IIb HDACs were also altered (p<0.05). Immunolocalizationstudies showed that HDAC1/2 were mainly expressed in primaryspermatocytes and H4ac was immunolocalized in late meiotic stagesin vehicle mice while it was detected in primary spermatocytesand in successive stages until round spermatid in cocaine-treatedmice. We observed altered mRNA expression of DNA methylationmarkers in isolated germ cells showing decreased levels of Dnmt3band Tet1 gene expression after cocaine treatment (p<0.05). TET1was mainly immunolocalized in primary spermatocytes in vehicleand cocaine-treated mice. The results presented here broaden thebasic knowledge of the impact of addictive stimulants on testicularpathophysiology, fertility and male reproductive health and implythat altered epigenetic homeostasis by cocaine may have potentialconsequences on future generations.
Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Gambini Pantoja, Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Vitullo, Alfredo Daniel. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bisagno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Gonzalez, Candela Rocio. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVI Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Asociación Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Asociación Argentina de Fisiología
Asociación Argentina de Virología
Asociación Argentina de Nanomedicinas
description Cocaine intake is associated with testicular toxicity and significantreproductive function impairment. There is accumulating evidencethat cocaine administration can trigger nongenetic inheritancethrough the male germ line affecting development and behavior ofthe offspring. The influence of environmental factors on the epigenomeof male germ cells appears to be most impactful if it happensduring a developmental phase when these cells are epigeneticallyreprogrammed. In the present study, we measured epigenetic marksin isolated germ cells of adult mice treated with cocaine (10 mg/kg) or vehicle, in an intermittent binge protocol (3 i.p. injections, 1h apart, one day on/off for 13 days). We found that chronic cocaineintake disrupts male germ cell epigenetic homeostasis, increasingglobal methylated citocine (5-mC) levels in DNA from germ cells andcauda epididymal sperm (germ cells: vehicle 13.15 ± 0.99 vs cocaine20.113 ± 2.28; sperm: vehicle 15.81 ± 1.08 vs cocaine 21.35± 1.52). Cocaine also increased acetylated histone 4 (H4ac) proteinlevels and decreased class I deacetylases HDAC1/2 mRNA andprotein expression (p<0.05). The mRNA expression levels of classIIa and IIb HDACs were also altered (p<0.05). Immunolocalizationstudies showed that HDAC1/2 were mainly expressed in primaryspermatocytes and H4ac was immunolocalized in late meiotic stagesin vehicle mice while it was detected in primary spermatocytesand in successive stages until round spermatid in cocaine-treatedmice. We observed altered mRNA expression of DNA methylationmarkers in isolated germ cells showing decreased levels of Dnmt3band Tet1 gene expression after cocaine treatment (p<0.05). TET1was mainly immunolocalized in primary spermatocytes in vehicleand cocaine-treated mice. The results presented here broaden thebasic knowledge of the impact of addictive stimulants on testicularpathophysiology, fertility and male reproductive health and implythat altered epigenetic homeostasis by cocaine may have potentialconsequences on future generations.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/199139
Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the sperm; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVI Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Asociación Argentina de Fisiología; Mar del Plata; Argentina; 2018; 105-105
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/199139
identifier_str_mv Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the sperm; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVI Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Asociación Argentina de Fisiología; Mar del Plata; Argentina; 2018; 105-105
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/reunion-anual
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundacion Revista Medicina
publisher.none.fl_str_mv Fundacion Revista Medicina
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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