Idiopathic male infertility and polymorphisms in the DNA methyltransferase genes involved in epigenetic marking

Qiuqin Tang,Wei Wu,Yiqiu Chen,Yankai Xia,Daozhen Chen,Xinru Wang,Hongjuan Ding

doi:10.1038/s41598-017-11636-9

Abstract

The purpose of this study was to investigate the association between male infertility and single-nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMT) genes (DNMT3B: rs2424909, DNMT1: rs4804490, DNMT3A: rs1550117 and DNMT3L: rs7354779). Eight hundred and thirty three idiopathic infertile males and four hundred and ten fertile controls from the hospitals affiliated to Nanjing Medical University between 2010 and 2012 were recruited in the study. We demonstrated a significantly increased risk of idiopathic infertility with abnormal semen parameters in association with the heterozygous genotype of variant rs4804490. Moreover, the AA genotype of variant rs4804490 was associated with significantly decreased risk for male infertility with abnormal semen parameters. A decreased risk of idiopathic infertility with abnormal semen parameters was associated with the homozygous genotype of variant rs2424909. These results suggested that variants in different DNMT genes have different relationships with idiopathic male infertility, and Chinese men carrying these variants have an increased or decreased risk of abnormal semen parameters.

Highlights

Male infertility is a heterogeneous disorder that contributes to the impairment of spermatogenesis
It has been identified that DNA methyltransferases (DNMT) play critical roles in spermatogenesis and male fertility, a genetic study of four DNMTs in idiopathic male infertility has not been performed yet
We have demonstrated a significantly increased risk of idiopathic male infertility with abnormal semen parameters in association with heterozygote of variant rs4804490, and a decreased risk of idiopathic infertility with abnormal semen parameters in association with variant homozygote of variant rs2424909 (P = 0.023 and 0.040, respectively)

Summary

Introduction

Male infertility is a heterogeneous disorder that contributes to the impairment of spermatogenesis. Mouse models have shown that aberrant DNA methylation patterns resulting from gene targeting of the DNMTs may cause spermatogenic defects[9,10,11,12]. Genes involved in the epigenetic pathways are likely to affect DNA methylation and are associated with male infertility. In addition to these active enzymes, the DNMT3L protein, catalytically inactive by itself, contributes to de novo methylation by interacting with the catalytic domains of DNMT3A and DNMT3B and enhancing their enzymatic activity[25,26,27]. To better understand the relationships between polymorphisms in DNMTs and idiopathic male infertility, we studied the associations between genetic variation in DNMT genes and altered semen parameters. We compared the transcriptional factors between C allele and T allele of rs2424909, C allele and the A allele of rs4804490

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Conclusion