Spermatozoa from infertile patients exhibit differences of DNA methylation associated with spermatogenesis-related processes: an array-based analysis.
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.
Genetics of Male Fertility Group, Unitat de Biologia Cel⋅lular (Facultat de Biociències), Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès) 08193, Spain.
Cristina
C
Camprubí
Genetics of Male Fertility Group, Unitat de Biologia Cel⋅lular (Facultat de Biociències), Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès) 08193, Spain.
Albert
A
Salas-Huetos
Sequentia Biotech, Edifici CRAG, Campus UAB, Bellaterra (Cerdanyola del Vallès) 08193, Spain.
Riccardo
R
Aiese-Cigliano
Genetics of Male Fertility Group, Unitat de Biologia Cel⋅lular (Facultat de Biociències), Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès) 08193, Spain.
Anna
A
Godo
Unidad de Reproducción Asistida de Centro Médico Teknon, Barcelona 08022, Spain.
Maria-Carme
MC
Pons
Departament d'Anatomia Patològica, Farmacologia i Microbiologia, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona 08036, Spain.
Giancarlo
G
Castellano
Unidad de Reproducción Asistida de Centro Médico Teknon, Barcelona 08022, Spain.
Mark
M
Grossmann
Sequentia Biotech, Edifici CRAG, Campus UAB, Bellaterra (Cerdanyola del Vallès) 08193, Spain.
Walter
W
Sanseverino
Departament d'Anatomia Patològica, Farmacologia i Microbiologia, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona 08036, Spain.
José I
JI
Martin-Subero
Laboratorio de Andrología y Banco de Semen, Instituto Universitario IVI Valencia, Valencia 46015, Spain.
Nicolás
N
Garrido
Genetics of Male Fertility Group, Unitat de Biologia Cel⋅lular (Facultat de Biociències), Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès) 08193, Spain. Electronic address: joan.blanco@uab.cat.
Joan
J
Blanco
D000328:Adult; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005298:Fertility / Q000235:genetics; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D009845:Oligospermia / Q000235:genetics; D011247:Pregnancy; D018873:Pregnancy Rate; D011401:Promoter Regions, Genetic; D012098:Reproduction; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism*; D055815:Young Adult
DNA methylation; age; assisted reproduction; epigenetics; male infertility; spermatozoa