Aberrant methylation of the TDMR of the GTF2AIL promoter does not affect fertilisation rates via TESE in patients with hypospermatogenesis

Increasing evidence shows a relationship between epigenetic regulation and male infertility. The GTF2A1L gene promoter contains the DNA methylation site of a tissue-specific differentially methylated region （TDMR）. Eighty-six patients with non-obstructive azoospermia were assessed for the DNA methylation state of CpG islands in the GTF2AIL promoter using testicular genomic DNA. Based on histological criteria, 26 of the 86 patients had normal spermatogenesis （controls）, 17 had hypospermatogenesis and 26 had a Sertoli cell-only phenotype or tubular sclerosis. GTF2AIL TDMR methylation was significantly lower in testes DNA from control samples than from hypospermatogenic samples （P=0.029）. Patients with hypospermatogenesis were divided into two subgroups： high DNA methylation （HM, n=5） and low DNA methylation （LM, n= 12）. The GTF2AIL TDMR methylation rate differed significantly between the HM and LM groups （P=0.0019）, and GTF2A 1L expression was significantly higher among the LM than in the HM patients （P=0.023）. High TDMR methylation was correlated with low GTF2AIL gene expression levels. Both groups demonstrated relatively good outcomes with respect to sperm retrieval, fertilisation, pregnancy and childbirth rates. We observed that aberrant GTF2AIL gene expression was not correlated with fertilisation rates. The testicular sperm extraction （TESE） technique may be used to overcome male infertility due to aberrant TDMR methvlation.

Phosphoribosyl-pyrophosphate synthetase 2 (PRPS2)depletion regulates spermatogenic cell apoptosis and is correlated with hypospermatogenesis

Phosphoribosyl-pyrophosphate synthetase 2(PRPS2)is a rate-limiting enzyme and plays an important role in purine and pyrimidine nucleotide synthesis.Recent studies report that PRPS2 is involved in male infertility.However,the role of PRPS2 in hypospermatogenesis is unknown.In this study,the relationship of PRPS2 with hypospermatogenesis and spermatogenic cell apoptosis was investigated.The results showed that PRPS2 depletion increased the number of apoptotic spermatogenic cells in vitro.PRPS2 was downregulated in a mouse model of hypospermatogenesis.When PRPS2 expression was knocked down in mouse testes,hypospermatogenesis and accelerated apoptosis of spermatogenic cells were noted.E2F transcription factor 1(E2F1)was confirmed as the target gene of PRPS2 and played a key role in cell apoptosis by regulating the P53/Bcl-xl/Bcl-2/Caspase 6/Caspase 9 apoptosis pathway.Therefore,these data indicate that PRPS2 depletion contributes to the apoptosis of spermatogenic cells and is associated with hypospermatogenesis,which may be helpful for the diagnosis of male infertility.