Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4

Autores
Carvajal, Guillermo; Brukman, Nicolás Gastón; Weigel Muñoz, Mariana; Battistone, Maria Agustina; Guazzone, Vanesa Anabella; Ikawa, Masahito; Haruhiko, Miyata; Lustig, Livia; Breton, Sylvie; Cuasnicu, Patricia Sara
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Epididymal Cysteine Rich Secretory Proteins 1 and 4 (CRISP1 and CRISP4) associate with sperm during maturation and play different roles in fertilization. However, males lacking each of these molecules individually are fertile, suggesting compensatory mechanisms between these homologous proteins. Based on this, in the present work, we generated double CRISP1/CRISP4 knockout (DKO) mice and examined their reproductive phenotype. Our data showed that the simultaneous lack of the two epididymal proteins results in clear fertility defects. Interestingly, whereas most of the animals exhibited specific sperm fertilizing ability defects supportive of the role of CRISP proteins in fertilization, one third of the males showed an unexpected epididymo-orchitis phenotype with altered levels of inflammatory molecules and non-viable sperm in the epididymis. Further analysis showed that DKO mice exhibited an immature epididymal epithelium and abnormal luminal pH, supporting these defects as likely responsible for the different phenotypes observed. These observations reveal that CRISP proteins are relevant for epididymal epithelium differentiation and male fertility, contributing to a better understanding of the fine-tuning mechanisms underlying sperm maturation and immunotolerance in the epididymis with clear implications for human epididymal physiology and pathology.
Fil: Carvajal, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Brukman, Nicolás Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Weigel Muñoz, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Battistone, Maria Agustina. Massachusetts General Hospital; Estados Unidos
Fil: Guazzone, Vanesa Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Ikawa, Masahito. Osaka University; Japón
Fil: Haruhiko, Miyata. Osaka University; Japón
Fil: Lustig, Livia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Breton, Sylvie. Massachusetts General Hospital; Estados Unidos
Fil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
FERTILITY
EPIDIDYMAL
CRISP
SPERM
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:11336/86913
Acceder
id CONICETDig_e05b5fc4e98a72189e934ecb520a6718
oai_identifier_str oai:ri.conicet.gov.ar:11336/86913
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4Carvajal, GuillermoBrukman, Nicolás GastónWeigel Muñoz, MarianaBattistone, Maria AgustinaGuazzone, Vanesa AnabellaIkawa, MasahitoHaruhiko, MiyataLustig, LiviaBreton, SylvieCuasnicu, Patricia SaraFERTILITYEPIDIDYMALCRISPSPERMhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Epididymal Cysteine Rich Secretory Proteins 1 and 4 (CRISP1 and CRISP4) associate with sperm during maturation and play different roles in fertilization. However, males lacking each of these molecules individually are fertile, suggesting compensatory mechanisms between these homologous proteins. Based on this, in the present work, we generated double CRISP1/CRISP4 knockout (DKO) mice and examined their reproductive phenotype. Our data showed that the simultaneous lack of the two epididymal proteins results in clear fertility defects. Interestingly, whereas most of the animals exhibited specific sperm fertilizing ability defects supportive of the role of CRISP proteins in fertilization, one third of the males showed an unexpected epididymo-orchitis phenotype with altered levels of inflammatory molecules and non-viable sperm in the epididymis. Further analysis showed that DKO mice exhibited an immature epididymal epithelium and abnormal luminal pH, supporting these defects as likely responsible for the different phenotypes observed. These observations reveal that CRISP proteins are relevant for epididymal epithelium differentiation and male fertility, contributing to a better understanding of the fine-tuning mechanisms underlying sperm maturation and immunotolerance in the epididymis with clear implications for human epididymal physiology and pathology.Fil: Carvajal, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Brukman, Nicolás Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Weigel Muñoz, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Battistone, Maria Agustina. Massachusetts General Hospital; Estados UnidosFil: Guazzone, Vanesa Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Ikawa, Masahito. Osaka University; JapónFil: Haruhiko, Miyata. Osaka University; JapónFil: Lustig, Livia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Breton, Sylvie. Massachusetts General Hospital; Estados UnidosFil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaNature Publishing Group2018-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/86913Carvajal, Guillermo; Brukman, Nicolás Gastón; Weigel Muñoz, Mariana; Battistone, Maria Agustina; Guazzone, Vanesa Anabella; et al.; Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4; Nature Publishing Group; Scientific Reports; 8; 1; 12-2018; 1-192045-23222045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-018-35719-3info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-018-35719-3info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30510210/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T10:36:23Zoai:ri.conicet.gov.ar:11336/86913instacron: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:34982025-11-05 10:36:23.625CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4
title Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4
spellingShingle Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4
Carvajal, Guillermo
FERTILITY
EPIDIDYMAL
CRISP
SPERM
title_short Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4
title_full Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4
title_fullStr Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4
title_full_unstemmed Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4
title_sort Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4
dc.creator.none.fl_str_mv Carvajal, Guillermo
Brukman, Nicolás Gastón
Weigel Muñoz, Mariana
Battistone, Maria Agustina
Guazzone, Vanesa Anabella
Ikawa, Masahito
Haruhiko, Miyata
Lustig, Livia
Breton, Sylvie
Cuasnicu, Patricia Sara
author Carvajal, Guillermo
author_facet Carvajal, Guillermo
Brukman, Nicolás Gastón
Weigel Muñoz, Mariana
Battistone, Maria Agustina
Guazzone, Vanesa Anabella
Ikawa, Masahito
Haruhiko, Miyata
Lustig, Livia
Breton, Sylvie
Cuasnicu, Patricia Sara
author_role author
author2 Brukman, Nicolás Gastón
Weigel Muñoz, Mariana
Battistone, Maria Agustina
Guazzone, Vanesa Anabella
Ikawa, Masahito
Haruhiko, Miyata
Lustig, Livia
Breton, Sylvie
Cuasnicu, Patricia Sara
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv FERTILITY
EPIDIDYMAL
CRISP
SPERM
topic FERTILITY
EPIDIDYMAL
CRISP
SPERM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Epididymal Cysteine Rich Secretory Proteins 1 and 4 (CRISP1 and CRISP4) associate with sperm during maturation and play different roles in fertilization. However, males lacking each of these molecules individually are fertile, suggesting compensatory mechanisms between these homologous proteins. Based on this, in the present work, we generated double CRISP1/CRISP4 knockout (DKO) mice and examined their reproductive phenotype. Our data showed that the simultaneous lack of the two epididymal proteins results in clear fertility defects. Interestingly, whereas most of the animals exhibited specific sperm fertilizing ability defects supportive of the role of CRISP proteins in fertilization, one third of the males showed an unexpected epididymo-orchitis phenotype with altered levels of inflammatory molecules and non-viable sperm in the epididymis. Further analysis showed that DKO mice exhibited an immature epididymal epithelium and abnormal luminal pH, supporting these defects as likely responsible for the different phenotypes observed. These observations reveal that CRISP proteins are relevant for epididymal epithelium differentiation and male fertility, contributing to a better understanding of the fine-tuning mechanisms underlying sperm maturation and immunotolerance in the epididymis with clear implications for human epididymal physiology and pathology.
Fil: Carvajal, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Brukman, Nicolás Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Weigel Muñoz, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Battistone, Maria Agustina. Massachusetts General Hospital; Estados Unidos
Fil: Guazzone, Vanesa Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Ikawa, Masahito. Osaka University; Japón
Fil: Haruhiko, Miyata. Osaka University; Japón
Fil: Lustig, Livia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Breton, Sylvie. Massachusetts General Hospital; Estados Unidos
Fil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Epididymal Cysteine Rich Secretory Proteins 1 and 4 (CRISP1 and CRISP4) associate with sperm during maturation and play different roles in fertilization. However, males lacking each of these molecules individually are fertile, suggesting compensatory mechanisms between these homologous proteins. Based on this, in the present work, we generated double CRISP1/CRISP4 knockout (DKO) mice and examined their reproductive phenotype. Our data showed that the simultaneous lack of the two epididymal proteins results in clear fertility defects. Interestingly, whereas most of the animals exhibited specific sperm fertilizing ability defects supportive of the role of CRISP proteins in fertilization, one third of the males showed an unexpected epididymo-orchitis phenotype with altered levels of inflammatory molecules and non-viable sperm in the epididymis. Further analysis showed that DKO mice exhibited an immature epididymal epithelium and abnormal luminal pH, supporting these defects as likely responsible for the different phenotypes observed. These observations reveal that CRISP proteins are relevant for epididymal epithelium differentiation and male fertility, contributing to a better understanding of the fine-tuning mechanisms underlying sperm maturation and immunotolerance in the epididymis with clear implications for human epididymal physiology and pathology.
publishDate 2018
dc.date.none.fl_str_mv 2018-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/86913
Carvajal, Guillermo; Brukman, Nicolás Gastón; Weigel Muñoz, Mariana; Battistone, Maria Agustina; Guazzone, Vanesa Anabella; et al.; Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4; Nature Publishing Group; Scientific Reports; 8; 1; 12-2018; 1-19
2045-2322
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/86913
identifier_str_mv Carvajal, Guillermo; Brukman, Nicolás Gastón; Weigel Muñoz, Mariana; Battistone, Maria Agustina; Guazzone, Vanesa Anabella; et al.; Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4; Nature Publishing Group; Scientific Reports; 8; 1; 12-2018; 1-19
2045-2322
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.nature.com/articles/s41598-018-35719-3
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-018-35719-3
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30510210/
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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
_version_ 1847978053559386112
score 13.121305

Publicaciones similares