Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility

STUDY QUESTION Are there DNA methylation alterations in sperm that could explain the reduced biological fertility of male partners from couples with unexplained infertility? SUMMARY ANSWER DNA methylation patterns, not only at specific loci but also at Alu Yb8 repetitive sequences, are altered in in...

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Detalles Bibliográficos
Autores: Urdinguio, Rocío G., Bayón, Gustavo F., Dmitrijeva, Marija, Toraño, Estela G., Bravo, Cristina, Fraga, Mario F., Bassas, Lluís, Larriba, Sara, Fernández, Agustín F.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2015
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/186633
Acceso en línea:https://hdl.handle.net/2445/186633
Access Level:acceso abierto
Palabra clave:Esterilitat masculina
Metilació
Male sterility
Methylation
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spelling Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertilityUrdinguio, Rocío G.Bayón, Gustavo F.Dmitrijeva, MarijaToraño, Estela G.Bravo, CristinaFraga, Mario F.Bassas, LluísLarriba, SaraFernández, Agustín F.Esterilitat masculinaMetilacióMale sterilityMethylationSTUDY QUESTION Are there DNA methylation alterations in sperm that could explain the reduced biological fertility of male partners from couples with unexplained infertility? SUMMARY ANSWER DNA methylation patterns, not only at specific loci but also at Alu Yb8 repetitive sequences, are altered in infertile individuals compared with fertile controls. STUDY DESIGN, SIZE, DURATION Case and control prospective study. This study compares 46 sperm samples obtained from 17 normospermic fertile men and 29 normospermic infertile patients. MAIN RESULTS AND THE ROLE OF CHANCE In this study we conduct, for the first time, a genome-wide study to identify alterations of sperm DNA methylation in individuals with unexplained infertility that may account for the differences in their biological fertility compared with fertile individuals. We have identified 2752 CpGs showing aberrant DNA methylation patterns, and more importantly, these differentially methylated CpGs were significantly associated with CpG sites which are specifically methylated in sperm when compared with somatic cells. We also found statistically significant (P < 0.001) associations between DNA hypomethylation and regions corresponding to those which, in somatic cells, are enriched in the repressive histone mark H3K9me3, and between DNA hypermethylation and regions enriched in H3K4me1 and CTCF, suggesting that the relationship between chromatin context and aberrant DNA methylation of sperm in infertile men could be locus-dependent. Finally, we also show that DNA methylation patterns, not only at specific loci but also at several repetitive sequences (LINE-1, Alu Yb8, NBL2, D4Z4), were lower in sperm than in somatic cells. Interestingly, sperm samples at Alu Yb8 repetitive sequences of infertile patients showed significantly lower DNA methylation levels than controls.Oxford University Press (OUP)2022202220152022info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion37 p.application/pdfhttps://hdl.handle.net/2445/186633Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésPostprint del document publicat a: https://doi.org/10.1093/humrep/dev053Human Reproduction, 2015, vol. 30, num. 5, p. 1014-1028https://doi.org/10.1093/humrep/dev053(c) Urdinguio, Rocio G. et al, 2015info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1866332026-05-29T05:05:01Z
dc.title.none.fl_str_mv Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility
title Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility
spellingShingle Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility
Urdinguio, Rocío G.
Esterilitat masculina
Metilació
Male sterility
Methylation
title_short Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility
title_full Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility
title_fullStr Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility
title_full_unstemmed Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility
title_sort Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility
dc.creator.none.fl_str_mv Urdinguio, Rocío G.
Bayón, Gustavo F.
Dmitrijeva, Marija
Toraño, Estela G.
Bravo, Cristina
Fraga, Mario F.
Bassas, Lluís
Larriba, Sara
Fernández, Agustín F.
author Urdinguio, Rocío G.
author_facet Urdinguio, Rocío G.
Bayón, Gustavo F.
Dmitrijeva, Marija
Toraño, Estela G.
Bravo, Cristina
Fraga, Mario F.
Bassas, Lluís
Larriba, Sara
Fernández, Agustín F.
author_role author
author2 Bayón, Gustavo F.
Dmitrijeva, Marija
Toraño, Estela G.
Bravo, Cristina
Fraga, Mario F.
Bassas, Lluís
Larriba, Sara
Fernández, Agustín F.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Esterilitat masculina
Metilació
Male sterility
Methylation
topic Esterilitat masculina
Metilació
Male sterility
Methylation
description STUDY QUESTION Are there DNA methylation alterations in sperm that could explain the reduced biological fertility of male partners from couples with unexplained infertility? SUMMARY ANSWER DNA methylation patterns, not only at specific loci but also at Alu Yb8 repetitive sequences, are altered in infertile individuals compared with fertile controls. STUDY DESIGN, SIZE, DURATION Case and control prospective study. This study compares 46 sperm samples obtained from 17 normospermic fertile men and 29 normospermic infertile patients. MAIN RESULTS AND THE ROLE OF CHANCE In this study we conduct, for the first time, a genome-wide study to identify alterations of sperm DNA methylation in individuals with unexplained infertility that may account for the differences in their biological fertility compared with fertile individuals. We have identified 2752 CpGs showing aberrant DNA methylation patterns, and more importantly, these differentially methylated CpGs were significantly associated with CpG sites which are specifically methylated in sperm when compared with somatic cells. We also found statistically significant (P < 0.001) associations between DNA hypomethylation and regions corresponding to those which, in somatic cells, are enriched in the repressive histone mark H3K9me3, and between DNA hypermethylation and regions enriched in H3K4me1 and CTCF, suggesting that the relationship between chromatin context and aberrant DNA methylation of sperm in infertile men could be locus-dependent. Finally, we also show that DNA methylation patterns, not only at specific loci but also at several repetitive sequences (LINE-1, Alu Yb8, NBL2, D4Z4), were lower in sperm than in somatic cells. Interestingly, sperm samples at Alu Yb8 repetitive sequences of infertile patients showed significantly lower DNA methylation levels than controls.
publishDate 2015
dc.date.none.fl_str_mv 2015
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/186633
url https://hdl.handle.net/2445/186633
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Postprint del document publicat a: https://doi.org/10.1093/humrep/dev053
Human Reproduction, 2015, vol. 30, num. 5, p. 1014-1028
https://doi.org/10.1093/humrep/dev053
dc.rights.none.fl_str_mv (c) Urdinguio, Rocio G. et al, 2015
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Urdinguio, Rocio G. et al, 2015
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 37 p.
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press (OUP)
publisher.none.fl_str_mv Oxford University Press (OUP)
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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