Abstract
Severe oligozoospermia (SO) is a complex disorder, whose etiology is the combined effect of genetic factors and epigenetic conditions. In this study, we examined DNA methylation and mRNA expression status in a set of testicular tissues of SO patients (n = 3), and compared methylated data with those derived from obstructive azoospermia (OA) patients (n = 3) with normal spermatogenesis phenotype. We identified 1,960 differentially methylated CpG sites showing significant alterations in SO vs. OA using the Illumina Infinium HumanMethylation450 bead array. By integrating above DNA methylation data and mRNA expression results, we totally identified 72 methylated CpG sites located in 65 genes with anti-correlation between DNA methylation and mRNA expression. Integrated pathways analysis indicates that these genes are involved in response to hormone stimulus, activation of protein kinase activity, and apoptotic process, among others. We also observed some genes with inversely correlated difference is novel in male infertility field, including PTPRN2, EPHX1, SERPINB9, SLIT3, etc. Our results lay a groundwork for further biological study of SO. Moreover, we generated a workflow for integrated analysis of DNA methylation and mRNA expression, which is expandable to other study types.
Highlights
Fertility is a major worldwide health problem and affects about 15% of couples, 40–50% of which are attributed to male factors (Anderson et al, 2009)
We propose an approach to common human disease that incorporates DNA methylation and mRNA expression profiles (Figure 1)
After filtering the raw data and statistical analysis, we determined that 1960 CpG sites, related to 1440 different genes, showing significant differences of DNA methylation in Severe oligozoospermia (SO), compared with controls
Summary
Fertility is a major worldwide health problem and affects about 15% of couples, 40–50% of which are attributed to male factors (Anderson et al, 2009). Genetic defects contribute to 15–30% cases of male infertility. Great attentions has been paid to the epigenetic studies due to the great achievement on the novel knowledge in the regulation of gene expression. In contrast to the definition of genetic defects that modify the DNA sequence itself, epigenetic defects are heritable alterations in the function of specific genes but not related to modification in the DNA sequence (Stuppia et al, 2015). DNA methylation is one of the most extensively investigated epigenetic mechanisms. DNA methylation is the stable, covalent addition of a methylgroup to 5′- position
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