Aberrant sperm DNA methylation predicts male fertility status and embryo quality.

Autor:	Aston KI; Department of Surgery, University of Utah Andrology and IVF Laboratories, University of Utah School of Medicine, Salt Lake City, Utah., Uren PJ; Molecular and Computational Biology, University of Southern California, Los Angeles, California., Jenkins TG; Department of Surgery, University of Utah Andrology and IVF Laboratories, University of Utah School of Medicine, Salt Lake City, Utah., Horsager A; Episona, Inc, Glendale, California., Cairns BR; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah; Howard Hughes Medical Institute, Chevy Chase, Maryland., Smith AD; Molecular and Computational Biology, University of Southern California, Los Angeles, California., Carrell DT; Department of Surgery, University of Utah Andrology and IVF Laboratories, University of Utah School of Medicine, Salt Lake City, Utah; Department of Obstetrics and Gynecology and Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah. Electronic address: douglas.carrell@hsc.utah.edu.
Jazyk:	angličtina
Zdroj:	Fertility and sterility [Fertil Steril] 2015 Dec; Vol. 104 (6), pp. 1388-97.e1-5. Date of Electronic Publication: 2015 Sep 08.
DOI:	10.1016/j.fertnstert.2015.08.019
Abstrakt:	Objective: To evaluate whether male fertility status and/or embryo quality during in vitro fertilization (IVF) therapy can be predicted based on genomewide sperm deoxyribonucleic acid (DNA) methylation patterns. Design: Retrospective cohort study. Setting: University-based fertility center. Patient(s): Participants were 127 men undergoing IVF treatment (where any major female factor cause of infertility had been ruled out), and 54 normozoospermic, fertile men. The IVF patients were stratified into 2 groups: patients who had generally good embryogenesis and a positive pregnancy (n = 55), and patients with generally poor embryogenesis (n = 72; 42 positive and 30 negative pregnancies) after IVF. Intervention(s): Genomewide sperm DNA methylation analysis was performed to measure methylation at >485,000 sites across the genome. Main Outcome Measure(s): A comparison was made of DNA methylation patterns of IVF patients vs. normozoospermic, fertile men. Result(s): Predictive models proved to be highly accurate in classifying male fertility status (fertile or infertile), with 82% sensitivity, and 99% positive predictive value. Hierarchic clustering identified clusters enriched for IVF patient samples and for poor-quality-embryo samples. Models built to identify samples within these groups, from neat samples, achieved positive predictive value ≥ 94% while identifying >one fifth of all IVF patient and poor-quality-embryo samples in each case. Using density gradient prepared samples, the same approach recovered 46% of poor-quality-embryo samples with no false positives. Conclusion(s): Sperm DNA methylation patterns differ significantly and consistently for infertile vs. fertile, normozoospermic men. In addition, DNA methylation patterns may be predictive of embryo quality during IVF. (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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