Incorrect DNA methylation of the DAZL promoter CpG island associates with defective human sperm  

Oleh:

Navarro-Costa, Paulo ; Nogueira, Paulo ; Carvalho, Marta

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Human Reproduction vol. 25 no. 10 (Oct. 2010), page 2647-2654.
Topik: * male infertility * spermatogenesis * epigenetics * DAZ gene family * DNA methylation

Ketersediaan

Perpustakaan FK Nomor Panggil: H07.K.2010.04 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

BACKGROUND Successful gametogenesis requires the establishment of an appropriate epigenetic state in developing germ cells. Nevertheless, an association between abnormal spermatogenesis and epigenetic disturbances in germline-specific genes remains to be demonstrated. METHODS In this study, the DNA methylation pattern of the promoter CpG island (CGI) of two germline regulator genes—DAZL and DAZ, was characterized by bisulphite genomic sequencing in quality-fractioned ejaculated sperm populations from normozoospermic (NZ) and oligoasthenoteratozoospermic (OAT) men. RESULTS OAT patients display increased methylation defects in the DAZL promoter CGI when compared with NZ controls. Such differences are recorded when analyzing sperm fractions enriched either in normal or defective germ cells (P< 0.001 in both cases). Significant differences in DNA methylation profiles are also observable when comparing the qualitatively distinct germ cell fractions inside the NZ and OAT groups (P= 0.003 and P= 0.007, respectively). Contrastingly, the unmethylation pattern of the DAZ promoter CGI remains correctly established in all experimental groups. CONCLUSIONS An association between disrupted DNA methylation of a key spermatogenesis gene and abnormal human sperm is described here for the first time. These results suggest that incorrect epigenetic marks in germline genes may be correlated with male gametogenic defects.

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