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Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm.

Houshdaran S, Cortessis VK, Siegmund K, Yang A, Laird PW, Sokol RZ - PLoS ONE (2007)

Bottom Line: This process involves widespread erasure of somatic-like patterns of DNA methylation followed by establishment of sex-specific patterns by de novo DNA methylation.This is the first report of a broad epigenetic defect associated with abnormal semen parameters.Our results suggest that the underlying mechanism for these epigenetic changes may be improper erasure of DNA methylation during epigenetic reprogramming of the male germ line.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.

ABSTRACT

Background: Male-factor infertility is a common condition, and etiology is unknown for a high proportion of cases. Abnormal epigenetic programming of the germline is proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. During germ cell maturation and gametogenesis, cells of the germ line undergo extensive epigenetic reprogramming. This process involves widespread erasure of somatic-like patterns of DNA methylation followed by establishment of sex-specific patterns by de novo DNA methylation. Incomplete reprogramming of the male germ line could, in theory, result in both altered sperm DNA methylation and compromised spermatogenesis.

Methodology/principal finding: We determined concentration, motility and morphology of sperm in semen samples collected by male members of couples attending an infertility clinic. Using MethyLight and Illumina assays we measured methylation of DNA isolated from purified sperm from the same samples. Methylation at numerous sequences was elevated in DNA from poor quality sperm.

Conclusions: This is the first report of a broad epigenetic defect associated with abnormal semen parameters. Our results suggest that the underlying mechanism for these epigenetic changes may be improper erasure of DNA methylation during epigenetic reprogramming of the male germ line.

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Related in: MedlinePlus

Box plots illustrating associations between semen parameters and level of methylation (PMR, on the natural-log scale) in DNA isolated from 65 study sperm samples.DNA methylation was measured by MethyLight. Methylation targets were sequences specific to the genes HRAS, NTF3, MT1A, PAX8, PLAGL1, DIRAS3, MEST and SFN and the repetitive element Satellite 2 (SAT2CHRM1). P-value for trend over category of semen parameter is given for each plot. Rows: DNA methylation targets; columns: semen parameters.
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pone-0001289-g001: Box plots illustrating associations between semen parameters and level of methylation (PMR, on the natural-log scale) in DNA isolated from 65 study sperm samples.DNA methylation was measured by MethyLight. Methylation targets were sequences specific to the genes HRAS, NTF3, MT1A, PAX8, PLAGL1, DIRAS3, MEST and SFN and the repetitive element Satellite 2 (SAT2CHRM1). P-value for trend over category of semen parameter is given for each plot. Rows: DNA methylation targets; columns: semen parameters.

Mentions: We evaluated 294 MethyLight reactions (Table S1A–B) for the presence of methylation in sperm DNA from an anonymous semen sample obtained from a sperm bank. The 35 selected reactions (Table S1A) were used to assay sperm DNA from 65 study samples. At many of the 35 sequences methylation levels were elevated in DNA from poor quality sperm. Striking associations with each of sperm concentration, motility and morphology were observed for four sequences: NTF3, MT1A, PAX8 and PLAGL1 (Figure 1).


Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm.

Houshdaran S, Cortessis VK, Siegmund K, Yang A, Laird PW, Sokol RZ - PLoS ONE (2007)

Box plots illustrating associations between semen parameters and level of methylation (PMR, on the natural-log scale) in DNA isolated from 65 study sperm samples.DNA methylation was measured by MethyLight. Methylation targets were sequences specific to the genes HRAS, NTF3, MT1A, PAX8, PLAGL1, DIRAS3, MEST and SFN and the repetitive element Satellite 2 (SAT2CHRM1). P-value for trend over category of semen parameter is given for each plot. Rows: DNA methylation targets; columns: semen parameters.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2100168&req=5

pone-0001289-g001: Box plots illustrating associations between semen parameters and level of methylation (PMR, on the natural-log scale) in DNA isolated from 65 study sperm samples.DNA methylation was measured by MethyLight. Methylation targets were sequences specific to the genes HRAS, NTF3, MT1A, PAX8, PLAGL1, DIRAS3, MEST and SFN and the repetitive element Satellite 2 (SAT2CHRM1). P-value for trend over category of semen parameter is given for each plot. Rows: DNA methylation targets; columns: semen parameters.
Mentions: We evaluated 294 MethyLight reactions (Table S1A–B) for the presence of methylation in sperm DNA from an anonymous semen sample obtained from a sperm bank. The 35 selected reactions (Table S1A) were used to assay sperm DNA from 65 study samples. At many of the 35 sequences methylation levels were elevated in DNA from poor quality sperm. Striking associations with each of sperm concentration, motility and morphology were observed for four sequences: NTF3, MT1A, PAX8 and PLAGL1 (Figure 1).

Bottom Line: This process involves widespread erasure of somatic-like patterns of DNA methylation followed by establishment of sex-specific patterns by de novo DNA methylation.This is the first report of a broad epigenetic defect associated with abnormal semen parameters.Our results suggest that the underlying mechanism for these epigenetic changes may be improper erasure of DNA methylation during epigenetic reprogramming of the male germ line.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.

ABSTRACT

Background: Male-factor infertility is a common condition, and etiology is unknown for a high proportion of cases. Abnormal epigenetic programming of the germline is proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. During germ cell maturation and gametogenesis, cells of the germ line undergo extensive epigenetic reprogramming. This process involves widespread erasure of somatic-like patterns of DNA methylation followed by establishment of sex-specific patterns by de novo DNA methylation. Incomplete reprogramming of the male germ line could, in theory, result in both altered sperm DNA methylation and compromised spermatogenesis.

Methodology/principal finding: We determined concentration, motility and morphology of sperm in semen samples collected by male members of couples attending an infertility clinic. Using MethyLight and Illumina assays we measured methylation of DNA isolated from purified sperm from the same samples. Methylation at numerous sequences was elevated in DNA from poor quality sperm.

Conclusions: This is the first report of a broad epigenetic defect associated with abnormal semen parameters. Our results suggest that the underlying mechanism for these epigenetic changes may be improper erasure of DNA methylation during epigenetic reprogramming of the male germ line.

Show MeSH
Related in: MedlinePlus