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  • Many studies have found that there


    Many studies have found that there is an aberrant DNA methylation in the imprinting control region of development-related genes in the spermatozoa of oligozoospermic men (Kobayashi et al, 2007, Marques et al, 2004, Marques et al, 2008), which most likely results from expressional changes in the DNMTs (). It should be kept in mind that since abnormal DNA methylation in the spermatozoa from oligozoospermic men would transmit its genomic content to fertilizable oocytes, it may negatively affect early development and results in abnormal growth (Filipponi and Feil, 2009). Similarly, if these sperm IFN-gamma, murine recombinant from oligozoospermic men were used in intra-cytoplasmic sperm injection, developmental outcome would be quite poor (Kobayashi et al., 2007). However, there is no investigation designed to examine the correlation between imprinting disorders and aberrant DNA methylation offspring of oligozoospermic men. Minor et al. (2011) reported that DNA methylation in the DMR region of the H19 gene is significantly decreased in the testicular sperm cells from obstructive azoospermia patients compared with fertile men (Minor et al., 2011) (). They also revealed that a similar decrease has been identified in the men undergoing reversal vasectomy in comparison with fertile men. These data show that aberrant DNA methylation or imprinting abnormalities seem to associate with the obstruction in the genital tract and can change the testicular microenvironment, ending with spermatogenetic failure. Pacheco et al. (2011) have found that 9189 CpG sites had different DNA methylation levels in the infertile patients, which can be associated with low-motility in the sperm samples when compared with fertile individuals (Pacheco et al., 2011). In that study, an increased DNMT3A expression has been detected in the sperm cells having low-motility and hypomethylated CpG sites (Pacheco et al., 2011). Aberrant DNA methylation has been defined in the definite imprinting genes such as H19, GTL2 (Gene trap locus 2), PEG1 (Paternally expressed genes 1), LIT1 (Long qT intronic transcript 1), ZAC (Sterile alpha motif and leucine zipper containing kinase AZK), PEG3 (Paternally expressed genes 3), SNRPN (Small nuclear ribonucleoprotein polypeptide N) in oligozoospermic patients, who have partial spermatogenesis failure (Boissonnas et al, 2010, Kobayashi et al, 2007, Marques et al, 2008). Besides, global methylation errors have been identified in the testicular cells obtained from azoospermic patients (Marques et al, 2010, Minor et al, 2011). The observed DNA methylation alterations in the imprinting genes most likely originates from changed DNMT expression, especially that of Dnmt3L and Dnmt3a gene because Dnmt3L and Dnmt3a knockout male mice models exhibit azoospermia and DNA methylation aberration (Bourc'his, Bestor, 2004, Kaneda et al, 2004) (). Similarly, hypomethylation of the paternally imprinted H19 gene in the oligozoospermic men might derive from impaired Dnmt3a and Dnmt3L gene expression (Marques et al., 2010). Ferfouri et al. (2013) demonstrated that there are 212 differentially methylated CpG sites in the testicular samples between obstructive azoospermia and non-obstructive azoospermia groups (Ferfouri et al., 2013). Overall, abnormal methylation at the imprinting genes in the spermatozoa from azoospermic patients seems to be associated with obstructive azoospermia and non-obstructive azoospermia development since the imprinting genes are largely methylated in the sperm samples from the obstructive azoospermia or non-obstructive azoospermia group (Marques et al., 2010). As DNMT1 is expressed in all human spermatogenetic cell types, it seems to be an important factor for normal spermatogenesis (Marques et al., 2011). Therefore, abnormal DNMT1 expression has been defined in the testicular tissues obtained from patients having spermatogenetic impairment and the similar issue was also observed in the mouse models (Takashima et al., 2009). The abnormal DNMT1 expression may also result from the presence of any mutation or polymorphism in the DNMT1 gene: such a study by Cheng et al. (2014), three exonic single nucleotide polymorphisms (SNP; rs16999593, rs2228612 and rs2228611) in the DNMT1 gene have been found to be related with development of severe oligospermia (Cheng et al., 2014). Additionally, Adiga et al. (2011) evaluated the DNMT3B gene expression in the spermatogenic cells at different stages of spermatogenesis in the fertile men and patients with bilateral spermatogenetic arrest (Adiga et al., 2011). They documented that DNMT3B is differentially expressed in the preleptotene/zygotene and pachytene spermatocytes from fertile and in infertile men. However, no remarkable expression difference for this gene is characterized in the elongated spermatids. Of note, although there are expressional differences in certain spermatogenic cells for the DNMT3B gene, the global DNA methylation do not exhibit any predominant discrepancy (Adiga et al., 2011).