DNA Methylation, as one of the epigenetic markers, isassociated with many disorders. In germ cells, methylation is involved in thesilencing of TEs, genomic imprinting, and DNA compaction. Early studies haveshown that there is an abnormal methylation in men with low sperm quality (31). These changes in genesinvolved in the processing of piRNAs can be associated with human spermatogenicdisorders. A recent study on peripheral blood samples of infertile men, showed that rs10773767 and rs6982089 were two single nucleotide polymorphisms (SNPs) in PIWIL1 andPIWIL2, respectively, and these polymorphisms were allele-specificmethylation-sensitive (32).
Thus, DNA methylationchanges in these genes are associated with spermatogenic disorders. Also, TDRD1(a Tudor-domain-containing protein ) which contributes to the MIWI function, someof its variants may be associated with a risk of defect in spermatogenesis andinfertility (33, 34). Additionally, Consideringthe relationship between the modified pattern of methylation of TEs and maleinfertility (34, 35), these alterations maybe due to changed expression of the piRNAs. These results show that the studyof methylation patterns in the pathways of piRNAs processing can help us betterunderstand the etiology of male infertility.
The targeting of piRNAs as novel therapies Theuse of piRNAs is one of the therapeutic approaches that can be used in manydisorders. Based on the roles of piRNAs and PIWI proteins, there are two approachesto change the expression of piRNAs: antibodies can be useful against PIWIproteins at post-translational levels, while artificial piRNAs are a goodoption for both transcriptional and post-translational approaches (Figure 3). Theanti-PIWI antibody prevents the formation of the piRISC complex, hence, thepiRNA expression can be changed. On the other hand, if the expression of apiRNA is reduced in a disorder, the transposon levels may be increased, in thiscase, the use of artificial piRNA is one of the approaches that can be used.
Also,in germ cells, transposons may alter the DNA methylation and inducingmethylation through artificial piRNAs could lead to gene silencing (36). Therefore, these are important in assessmentof hereditary epigenetic alterations. However, these new approaches are in theearly stages and require more extensive research.