Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with abnormal chromatin packaging or poor in vitro fertilization embryogenesis

Genome-wide sperm DNA methylation patterns were evaluated in abnormal protamine 1/protamine 2 ratio, abnormal IVF/intracytoplasmic sperm injection embryogenesis, and normozoospermic, fertile control men. Broadly aberrant methylation was observed in three patients.

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Authors

Kenneth I. Aston, Ph.D., Vasu Punj, Ph.D., Lihua Liu, M.D., Douglas T. Carrell, Ph.D.

Volume 97, Issue 2 , Pages 285-292.e4

Abstract

Objective:

To evaluate genome-wide DNA methylation patterns in sperm from men with abnormal sperm chromatin packaging and patients displaying abnormal embryogenesis after IVF in the absence of known female factors.

Design:

Case–control study.

Setting:

University andrology and research laboratory.

Patient(s):

Men with abnormally high and low protamine 1/protamine 2 ratio (n = 15); patients who have undergone IVF/intracytoplasmic sperm injection resulting in abnormal embryogenesis (n = 13); and normozoospermic, fertile controls (n = 15).

Intervention(s):

Genome-wide sperm DNA methylation was measured using the Illumina Infinium HumanMethylation27 BeadChip assay. Follow-up targeted methylation analysis was performed using bisulfite pyrosequencing.

Main Outcome Measure(s):

Methylation levels at more than 27,000 CpGs genome-wide were compared between groups.

Result(s):

Of the 43 men analyzed, 40 displayed highly concordant methylation patterns; however, two men with abnormal protamine 1/protamine 2 and one abnormal embryogenesis patient displayed significantly altered methylation patterns across a large number of CpGs. Imprinted regions were more prone to deregulation than the genome at large.

Conclusion(s):

We have identified three individuals displaying broad disruption of sperm DNA methylation profiles. Although the sample set analyzed is relatively small, these results indicate that broad disruptions in sperm DNA methylation may be an important signature in some infertile men. Functional studies will be necessary to characterize the developmental consequences of such epigenetic disruption.

Read the full text at: http://www.fertstert.org/article/S0015-0282(11)02762-2/fulltext

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Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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