Spermatozoa from infertile patients exhibit differences of DNA methylation associated with spermatogenesis-related processes: an array-based analysis

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• 作者：Cristina Camprubí ; ^a ; ¹Author Vitae ; Albert Salas-Huetos^a ; Riccardo Aiese-Cigliano^b ; Anna Godo^a ; Maria-Carme Pons^c ; Giancarlo Castellano^d ; Mark Grossmann^c ; ² ; Walter Sanseverino^b ; José ; I. Martin-Subero^d ; Nicolá ; s Garrido^e ; Joan Blanco^a ; ^{joan.blanco@uab.cat}
• 关键词：age ; assisted reproduction ; DNA methylation ; epigenetics ; male infertility ; spermatozoa
• 刊名：Reproductive BioMedicine Online
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：33
• 期：6
• 页码：709-719
• 全文大小：2744 K
• 卷排序：33

文摘

The influence of aberrant sperm DNA methylation on the reproductive capacity of couples has been postulated as a cause of infertility. This study compared the DNA methylation of spermatozoa of 19 fertile donors and 42 infertile patients using the Illumina 450K array. Clustering analysis of methylation data arranged fertile and infertile patients into two groups. Bivariate clustering analysis identified a differential distribution of samples according to the characteristics of seminogram and age, suggesting a possible link between these parameters and specific methylation profiles. The study identified 696 differentially methylated cytosine-guanine dinucleotides (CpG) associated with 501 genes between fertile donors and infertile patients. Ontological enrichment analysis revealed 13 processes related to spermatogenesis. Data filtering identified a set of 17 differentially methylated genes, some of which had functions relating to spermatogenesis. A significant association was identified between RPS6KA2 hypermethylation and advanced age (P = 0.016); APCS hypermethylation and oligozoospermia (P = 0.041); JAM3/NCAPD3 hypermethylation and numerical chromosome sperm anomalies (P = 0.048); and ANK2 hypermethylation and lower pregnancy rate (P = 0.040). This description of a set of differentially methylated genes provides a framework for further investigation into the influence of such variation in male fertility in larger patient cohorts.