Tissue-specific differentially methylated regions of the human VASA gene are potentially associated with maturation arrest phenotype in the testis

Numerous CpG islands containing tissue-specific differentially methylated regions (TDMRs) are potential methylation sites in normal cells and tissues. The VASA (also known as DDX4) gene is believed to be under the control of TDMRs. A total of 131 male patients with idiopathic azoospermia or severe oligospermia were evaluated histologically, and the methylation status of CpG islands in the VASA gene was screened. Genome DNAs were obtained from testicular biopsy and modified with sodium bisulfite, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied. This system is capable of analyzing both the methylated and unmethylated CpG island in the genome. The methylation analysis is conducted by an epigram as graphic data. On histological assessment, 17 of 131 patients revealed maturation arrest (MA). In all, 6 of the 17 patients showed particularly high VASA TDMR methylation rates, whereas the remaining 11 patients and controls had low methylation rates. This study may imply that the VASA TDMR methylation is significantly higher among patients with MA, in whom the VASA gene expression was silenced. This finding represents an important contribution to the molecular basis of meiotic arrest as one possible cause of idiopathic infertility. Journal of Human Genetics (2009) 54, 450-456; doi: 10.1038/jhg.2009.59; published online 24 July 2009