• PMID: 24524831
• Gene Name: PIWIL2
• Condition: Male infertility, Spermatogenetic defects
• Association: The study identifies surrogate DNA methylation markers for idiopathic infertility in peripheral blood and suggests that allele-specific DNA methylation differences at regulatory sites of genes involved in piRNA regulation are associated with disturbed spe
• Population size: 40
• Population details: 40 (30 infertile men with normal CFTR and AZF tests and karyotype, 10 fertile male controls)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility, Spermatogenetic defects

Array-based DNA methylation profiling in male infertility reveals allele-specific DNA methylation in PIWIL1 and PIWIL2

Friemel C, Ammerpohl O, Gutwein J, Schmutzler AG, Caliebe A, Kautza M, von Otte S, Siebert R, Bens S.

OBJECTIVE: To identify CpG sites differentially methylated in peripheral blood of men with idiopathic infertility due to impaired spermatogenesis as compared with fertile controls. DESIGN: DNA methylation profiling on peripheral blood samples using the HumanMethylation450 BeadChip (Illumina) in patients and controls, single-nucleotide polymorphism (SNP) typing by Sanger sequencing. SETTING: University institute in cooperation with genetic and infertility clinics. PATIENT(S): 30 infertile men with normal CFTR and AZF tests and karyotype, and 10 fertile male controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): DNA methylation levels at CpG sites. RESULT(S): We identified 471 CpGs (287 genes) as differentially methylated between patients and controls. These were significantly enriched for the gene ontology functions MHC class II receptor activity and piwi-interacting (piRNA) binding. The latter was associated with two methylation-sensitive SNPs in the genes PIWIL1 and PIWIL2, respectively, which showed significant allele distribution skewing in the infertile cohort. We found that 445 (94.5%) of 471 differentially methylated CpGs were associated with SNPs, but 26 (15 genes) were not genomically templated, including the ENO1, MTA2, BRSK2, and LBX2 genes previously associated with fertility and spermatogenesis. CONCLUSION(S): Our study identifies surrogate DNA methylation markers for idiopathic infertility in peripheral blood and suggests that allele-specific DNA methylation differences at regulatory sites of genes involved in piRNA regulation are associated with disturbed spermatogenesis. CI - Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. FAU - Friemel, Carolin AU - Friemel C AD - Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. FAU - Ammerpohl, Ole AU - Ammerpohl O AD - Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. FAU - Gutwein, Jana AU - Gutwein J AD - Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. FAU - Schmutzler, Andreas G AU - Schmutzler AG AD - Department of Gynecology and Obstetrics, Center of Reproductive Medicine, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. FAU - Caliebe, Almuth AU - Caliebe A AD - Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. FAU - Kautza, Monika AU - Kautza M AD - Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. FAU - von Otte, Sören AU - von Otte S AD - Department of Gynecology and Obstetrics, Center of Reproductive Medicine, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. FAU - Siebert, Reiner AU - Siebert R AD - Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.