Epigenetic disruption of the PIWI pathway in human spermatogenic disorders.

Epigenetic changes are involved in a wide range of common human diseases. Although DNA methylation defects are known to be associated with male infertility in mice, their impact on human deficiency of sperm production has yet to be determined. We have assessed the global genomic DNA methylation prof...

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Autores principales:	Holger Heyn, Humberto J Ferreira, Lluís Bassas, Sandra Bonache, Sergi Sayols, Juan Sandoval, Manel Esteller, Sara Larriba
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2d445a8cd264478d80689641129ff52f
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spelling	oai:doaj.org-article:2d445a8cd264478d80689641129ff52f2021-11-18T08:11:09ZEpigenetic disruption of the PIWI pathway in human spermatogenic disorders.1932-620310.1371/journal.pone.0047892https://doaj.org/article/2d445a8cd264478d80689641129ff52f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23112866/?tool=EBIhttps://doaj.org/toc/1932-6203Epigenetic changes are involved in a wide range of common human diseases. Although DNA methylation defects are known to be associated with male infertility in mice, their impact on human deficiency of sperm production has yet to be determined. We have assessed the global genomic DNA methylation profiles in human infertile male patients with spermatogenic disorders by using the Infinium Human Methylation27 BeadChip. Three populations were studied: conserved spermatogenesis, spermatogenic failure due to germ cell maturation defects, and Sertoli cell-only syndrome samples. A disease-associated DNA methylation profile, characterized by targeting members of the PIWI-associated RNA (piRNA) processing machinery, was obtained. Bisulfite genomic sequencing and pyrosequencing in a large cohort (n = 46) of samples validated the altered DNA methylation patterns observed in piRNA-processing genes. In particular, male infertility was associated with the promoter hypermethylation-associated silencing of PIWIL2 and TDRD1. The downstream effects mediated by the epigenetic inactivation of the PIWI pathway genes were a defective production of piRNAs and a hypomethylation of the LINE-1 repetitive sequence in the affected patients. Overall, our data suggest that DNA methylation, at least that affecting PIWIL2/TDRD1, has a role in the control of gene expression in spermatogenesis and its imbalance contributes to an unsuccessful germ cell development that might explain a group of male infertility disorders.Holger HeynHumberto J FerreiraLluís BassasSandra BonacheSergi SayolsJuan SandovalManel EstellerSara LarribaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e47892 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Holger Heyn Humberto J Ferreira Lluís Bassas Sandra Bonache Sergi Sayols Juan Sandoval Manel Esteller Sara Larriba Epigenetic disruption of the PIWI pathway in human spermatogenic disorders.
description	Epigenetic changes are involved in a wide range of common human diseases. Although DNA methylation defects are known to be associated with male infertility in mice, their impact on human deficiency of sperm production has yet to be determined. We have assessed the global genomic DNA methylation profiles in human infertile male patients with spermatogenic disorders by using the Infinium Human Methylation27 BeadChip. Three populations were studied: conserved spermatogenesis, spermatogenic failure due to germ cell maturation defects, and Sertoli cell-only syndrome samples. A disease-associated DNA methylation profile, characterized by targeting members of the PIWI-associated RNA (piRNA) processing machinery, was obtained. Bisulfite genomic sequencing and pyrosequencing in a large cohort (n = 46) of samples validated the altered DNA methylation patterns observed in piRNA-processing genes. In particular, male infertility was associated with the promoter hypermethylation-associated silencing of PIWIL2 and TDRD1. The downstream effects mediated by the epigenetic inactivation of the PIWI pathway genes were a defective production of piRNAs and a hypomethylation of the LINE-1 repetitive sequence in the affected patients. Overall, our data suggest that DNA methylation, at least that affecting PIWIL2/TDRD1, has a role in the control of gene expression in spermatogenesis and its imbalance contributes to an unsuccessful germ cell development that might explain a group of male infertility disorders.
format	article
author	Holger Heyn Humberto J Ferreira Lluís Bassas Sandra Bonache Sergi Sayols Juan Sandoval Manel Esteller Sara Larriba
author_facet	Holger Heyn Humberto J Ferreira Lluís Bassas Sandra Bonache Sergi Sayols Juan Sandoval Manel Esteller Sara Larriba
author_sort	Holger Heyn
title	Epigenetic disruption of the PIWI pathway in human spermatogenic disorders.
title_short	Epigenetic disruption of the PIWI pathway in human spermatogenic disorders.
title_full	Epigenetic disruption of the PIWI pathway in human spermatogenic disorders.
title_fullStr	Epigenetic disruption of the PIWI pathway in human spermatogenic disorders.
title_full_unstemmed	Epigenetic disruption of the PIWI pathway in human spermatogenic disorders.
title_sort	epigenetic disruption of the piwi pathway in human spermatogenic disorders.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2d445a8cd264478d80689641129ff52f
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Epigenetic disruption of the PIWI pathway in human spermatogenic disorders.

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