title: Aberrant methylation of the TDMR of the GTF2A1L promoter does not affect fertilisation rates via TESE in patients with hypospermatogenesis.
abstract: 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 GTF2A1L 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. GTF2A1L 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 GTF2A1L TDMR methylation rate differed significantly between the HM and LM groups (P=0.0019), and GTF2A1L expression was significantly higher among the LM than in the HM patients (P=0.023). High TDMR methylation was correlated with low GTF2A1L gene expression levels. Both groups demonstrated relatively good outcomes with respect to sperm retrieval, fertilisation, pregnancy and childbirth rates. We observed that aberrant GTF2A1L 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 methylation.
authors.affiliation: Departments of Integrative Cancer Therapy and Urology, Andrology Unit, Kanazawa University Graduate School of Medical Science, Takara, Kanazawa, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Eitetsu
authors.initials: E
authors.lastname: Koh
authors.forename: Masashi
authors.initials: M
authors.lastname: Iijima
authors.forename: Masaki
authors.initials: M
authors.lastname: Taya
authors.forename: Yuji
authors.initials: Y
authors.lastname: Maeda
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
mesh_terms: D053713:Azoospermia / Q000235:genetics*; D018899:CpG Islands / Q000502:physiology; D019175:DNA Methylation; D006801:Humans; D008297:Male; D009845:Oligospermia / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000502:physiology*; D053625:Sperm Retrieval; D013091:Spermatogenesis / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C119951:GTF2A1L protein, human; D014157:Transcription Factors