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

REPRODUCTIVE BIOMEDICINE ONLINE

卷:33

Article

Camprubi, Cristina^1,6  Salas-Huetos, Albert¹  Aiese-Cigliano, Riccardo²  Godo, Anna¹  Pons, Maria-Carme³  Castellano, Giancarlo⁴  Grossmann, Mark^3,7  Sanseverino, Walter²  Martin-Subero, Jose I.⁴  Garrido, Nicolas⁵  Blanco, Joan¹ 

[1] Univ Autonoma Barcelona, Fac Biociencies, Genet Male Fertil Grp, Unitat Biol Cellular, Bellaterra 08193, Cerdanyola Del, Spain

[2] Sequentia Biotech, Edifici CRAG,Campus UAB, Bellaterra 08193, Cerdanyola Del, Spain

[3] Ctr Med Teknon, Unidad Reprod Asistida, Barcelona 08022, Spain

[4] Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Dept Anat Patol Farmacol & Microbiol, E-08036 Barcelona, Spain

[5] Inst Univ IVI Valencia, Lab Androl & Banco Semen, Valencia 46015, Spain

[6] GenIntegral, Barcelona, Spain

[7] Barcelona IVF, Barcelona 08017, Spain

关键词: age;    assisted reproduction;    DNA methylation;    epigenetics;    male infertility;    spermatozoa;   

DOI  :  10.1016/j.rbmo.2016.09.001

来源: Elsevier

【 摘 要 】

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. (C) 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

【 授权许可】

Free