title: Methylation status of imprinted genes and repetitive elements in sperm DNA from infertile males.
abstract: Stochastic, environmentally and/or genetically induced disturbances in the genome-wide epigenetic reprogramming processes during male germ-cell development may contribute to male infertility. To test this hypothesis, we have studied the methylation levels of 2 paternally (H19 and GTL2) and 5 maternally methylated (LIT1, MEST, NESPAS, PEG3, and SNRPN) imprinted genes, as well as of ALU and LINE1 repetitive elements in 141 sperm samples, which were used for assisted reproductive technologies (ART), including 106 couples with strictly male-factor or combined male and female infertility and 28 couples with strictly female-factor infertility. Aberrant methylation imprints showed a significant association with abnormal semen parameters, but did not seem to influence ART outcome. Repeat methylation also differed significantly between sperm samples from infertile and presumably fertile males. However, in contrast to imprinted genes, ALU methylation had a significant impact on pregnancy and live-birth rate in couples with male-factor or combined infertility. ALU methylation was significantly higher in sperm samples leading to pregnancy and live-birth than in those that did not. Sperm samples leading to abortions showed significantly lower ALU methylation levels than those leading to the birth of a baby.
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: El Hajj
authors.forename: U
authors.initials: U
authors.lastname: Zechner
authors.forename: E
authors.initials: E
authors.lastname: Schneider
authors.forename: A
authors.initials: A
authors.lastname: Tresch
authors.forename: J
authors.initials: J
authors.lastname: Gromoll
authors.forename: T
authors.initials: T
authors.lastname: Hahn
authors.forename: M
authors.initials: M
authors.lastname: Schorsch
authors.forename: T
authors.initials: T
authors.lastname: Haaf
mesh_terms: D000328:Adult; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics / Q000502:physiology*; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008297:Male; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D011247:Pregnancy; D011506:Proteins / Q000235:genetics; D062085:RNA, Long Noncoding; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism*; D055517:snRNP Core Proteins / Q000235:genetics
chemical_list: C485621:KCNQ1OT1 long non-coding RNA, human; D051741:Kruppel-Like Transcription Factors; C498907:MEG3 non-coding RNA, human; C490820:PEG3 protein, human; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins; D062085:RNA, Long Noncoding; C103637:mesoderm specific transcript protein; D055517:snRNP Core Proteins; D004247:DNA