Journal
REPRODUCTIVE BIOLOGY
Volume 17, Issue 3, Pages 246-251Publisher
INST ANIMAL REPRODUCTION FOOD RESEARCH
DOI: 10.1016/j.repbio.2017.05.010
Keywords
CpGs; DNA methylation; Sperm; Subfertility
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Infertility affects about 15% of couples worldwide, with approximately 7% of males suffering from infertility problems. This study was designed to assess the relationship between alterations in sperm DNA methylation patterns and semen parameters in subfertile males. Of a total of 108 males, 30 samples were subjected to 450 K BeadChip arrays to evaluate the variation in DNA methylation level between cases and controls. Three CpG sites showed the highest difference in methylation levels (cg09737095, cg14271023, and cg17662493), which are located in the KCNJ5, MLPH, and SMC1 beta genes, respectively; these were selected for further analysis using deep bisulfite sequencing in 78 independent samples (21 proven fertile controls, and 57 subfertile cases). The results of a validation study showed that variation in methylation levels was found in more than one CpG site: there was a significant decrease in methylation levels at six CpGs (CpG1, CpG3, CpG4, CpG6, CpG7, and CpG8) in the KCNJ5 gene-related amplicon (p <= 0.001, p <= 0.009. p <= 0.007, p <= 0.007, p <= 0.020, and p <= 0.016, respectively), and at (CpG1, CpG2, and CpG4) in the MLPH gene-related amplicon (p <= 0.003. p <= 0.005, and p <= 0.0001, respectively), while there was a significant increase in the methylation level at six out of eight CpGs in the SMC1 beta gene related amplicon in cases compared to controls. Our results show that three CpGs have a significant difference in sperm DNA methylation levels in subfertile males compared to proven fertile males. (C) 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Sp. z o.o. All rights reserved.
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