Unraveling epigenomic abnormality in azoospermic human males by WGBS, RNA-Seq, and transcriptome profiling analyses.

Purpose: To determine associations between genomic DNA methylation in testicular cells and azoospermia in human males.

Methods: This was a case-control study investigating the differences and conservations in DNA methylation, genome-wide DNA methylation, and bulk RNA-Seq for transcriptome profiling using testicular biopsy tissues from NOA and OA patients. Differential methylation and different conserved methylation regions associated with azoospermia were identified by comparing genomic DNA methylation of testicular seminiferous cells derived from NOA and OA patients.

Results: The genome methylation modification of testicular cells from NOA patients was disordered, and the reproductive-related gene expression was significantly different.

Conclusion: Our findings not only provide valuable knowledge of human spermatogenesis but also paved the way for the identification of genes/proteins involved in male germ cell development. The approach presented in this report provides a powerful tool to identify responsible biomolecules, and/or cellular changes (e.g., epigenetic abnormality) that induce male reproductive dysfunction such as OA and NOA.