Cargando…

Idiopathic Male Infertility Is Strongly Associated with Aberrant Promoter Methylation of Methylenetetrahydrofolate Reductase (MTHFR)

BACKGROUND: Abnormal germline DNA methylation in males has been proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. Previous studies have been focused on imprinted genes with DNA methylation in poor quality human sperms. However,...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Wei, Shen, Ouxi, Qin, Yufeng, Niu, Xiaobing, Lu, Chuncheng, Xia, Yankai, Song, Ling, Wang, Shoulin, Wang, Xinru
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976703/
https://www.ncbi.nlm.nih.gov/pubmed/21085488
http://dx.doi.org/10.1371/journal.pone.0013884
_version_ 1782190999270850560
author Wu, Wei
Shen, Ouxi
Qin, Yufeng
Niu, Xiaobing
Lu, Chuncheng
Xia, Yankai
Song, Ling
Wang, Shoulin
Wang, Xinru
author_facet Wu, Wei
Shen, Ouxi
Qin, Yufeng
Niu, Xiaobing
Lu, Chuncheng
Xia, Yankai
Song, Ling
Wang, Shoulin
Wang, Xinru
author_sort Wu, Wei
collection PubMed
description BACKGROUND: Abnormal germline DNA methylation in males has been proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. Previous studies have been focused on imprinted genes with DNA methylation in poor quality human sperms. However, recent but limited data have revealed that sperm methylation abnormalities may involve large numbers of genes or shown that genes that are not imprinted are also affected. METHODOLOGY/PRINCIPAL FINDINGS: Using the methylation-specific polymerase chain reaction and bisulfite sequencing method, we examined methylation patterns of the promoter of methylenetetrahydrofolate reductase (MTHFR) gene (NG_013351: 1538–1719) in sperm DNA obtained from 94 idiopathic infertile men and 54 normal fertile controls. Subjects with idiopathic infertility were further divided into groups of normozoospermia and oligozoospermia. Overall, 45% (41/94) of idiopathic infertile males had MTHFR hypermethylation (both hemimethylation and full methylation), compared with 15% of fertile controls (P<0.05). Subjects with higher methylation level of MTHFR were more likely to have idiopathic male infertility (P-value for trend  = 0.0007). Comparing the two groups of idiopathic infertile subjects with different sperm concentrations, a higher methylation pattern was found in the group with oligozoospermia. CONCLUSIONS: Hypermethylation of the promoter of MTHFR gene in sperms is associated with idiopathic male infertility. The functional relevance of hypermathylation of MTHFR to male fertility warrants further investigation.
format Text
id pubmed-2976703
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-29767032010-11-17 Idiopathic Male Infertility Is Strongly Associated with Aberrant Promoter Methylation of Methylenetetrahydrofolate Reductase (MTHFR) Wu, Wei Shen, Ouxi Qin, Yufeng Niu, Xiaobing Lu, Chuncheng Xia, Yankai Song, Ling Wang, Shoulin Wang, Xinru PLoS One Research Article BACKGROUND: Abnormal germline DNA methylation in males has been proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. Previous studies have been focused on imprinted genes with DNA methylation in poor quality human sperms. However, recent but limited data have revealed that sperm methylation abnormalities may involve large numbers of genes or shown that genes that are not imprinted are also affected. METHODOLOGY/PRINCIPAL FINDINGS: Using the methylation-specific polymerase chain reaction and bisulfite sequencing method, we examined methylation patterns of the promoter of methylenetetrahydrofolate reductase (MTHFR) gene (NG_013351: 1538–1719) in sperm DNA obtained from 94 idiopathic infertile men and 54 normal fertile controls. Subjects with idiopathic infertility were further divided into groups of normozoospermia and oligozoospermia. Overall, 45% (41/94) of idiopathic infertile males had MTHFR hypermethylation (both hemimethylation and full methylation), compared with 15% of fertile controls (P<0.05). Subjects with higher methylation level of MTHFR were more likely to have idiopathic male infertility (P-value for trend  = 0.0007). Comparing the two groups of idiopathic infertile subjects with different sperm concentrations, a higher methylation pattern was found in the group with oligozoospermia. CONCLUSIONS: Hypermethylation of the promoter of MTHFR gene in sperms is associated with idiopathic male infertility. The functional relevance of hypermathylation of MTHFR to male fertility warrants further investigation. Public Library of Science 2010-11-09 /pmc/articles/PMC2976703/ /pubmed/21085488 http://dx.doi.org/10.1371/journal.pone.0013884 Text en Wu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wu, Wei
Shen, Ouxi
Qin, Yufeng
Niu, Xiaobing
Lu, Chuncheng
Xia, Yankai
Song, Ling
Wang, Shoulin
Wang, Xinru
Idiopathic Male Infertility Is Strongly Associated with Aberrant Promoter Methylation of Methylenetetrahydrofolate Reductase (MTHFR)
title Idiopathic Male Infertility Is Strongly Associated with Aberrant Promoter Methylation of Methylenetetrahydrofolate Reductase (MTHFR)
title_full Idiopathic Male Infertility Is Strongly Associated with Aberrant Promoter Methylation of Methylenetetrahydrofolate Reductase (MTHFR)
title_fullStr Idiopathic Male Infertility Is Strongly Associated with Aberrant Promoter Methylation of Methylenetetrahydrofolate Reductase (MTHFR)
title_full_unstemmed Idiopathic Male Infertility Is Strongly Associated with Aberrant Promoter Methylation of Methylenetetrahydrofolate Reductase (MTHFR)
title_short Idiopathic Male Infertility Is Strongly Associated with Aberrant Promoter Methylation of Methylenetetrahydrofolate Reductase (MTHFR)
title_sort idiopathic male infertility is strongly associated with aberrant promoter methylation of methylenetetrahydrofolate reductase (mthfr)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976703/
https://www.ncbi.nlm.nih.gov/pubmed/21085488
http://dx.doi.org/10.1371/journal.pone.0013884
work_keys_str_mv AT wuwei idiopathicmaleinfertilityisstronglyassociatedwithaberrantpromotermethylationofmethylenetetrahydrofolatereductasemthfr
AT shenouxi idiopathicmaleinfertilityisstronglyassociatedwithaberrantpromotermethylationofmethylenetetrahydrofolatereductasemthfr
AT qinyufeng idiopathicmaleinfertilityisstronglyassociatedwithaberrantpromotermethylationofmethylenetetrahydrofolatereductasemthfr
AT niuxiaobing idiopathicmaleinfertilityisstronglyassociatedwithaberrantpromotermethylationofmethylenetetrahydrofolatereductasemthfr
AT luchuncheng idiopathicmaleinfertilityisstronglyassociatedwithaberrantpromotermethylationofmethylenetetrahydrofolatereductasemthfr
AT xiayankai idiopathicmaleinfertilityisstronglyassociatedwithaberrantpromotermethylationofmethylenetetrahydrofolatereductasemthfr
AT songling idiopathicmaleinfertilityisstronglyassociatedwithaberrantpromotermethylationofmethylenetetrahydrofolatereductasemthfr
AT wangshoulin idiopathicmaleinfertilityisstronglyassociatedwithaberrantpromotermethylationofmethylenetetrahydrofolatereductasemthfr
AT wangxinru idiopathicmaleinfertilityisstronglyassociatedwithaberrantpromotermethylationofmethylenetetrahydrofolatereductasemthfr