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Publication
Incorrect DNA methylation of the DAZL promoter CpG island associates with defective human sperm
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Advisor(s)
Abstract(s)
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 ¼ 0.003 and P ¼ 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.
Description
Versão impressa: Hum Reprod. 2010 Oct;25(10):2647-54
Keywords
Male infertility Spermatogenesis Epigenetics DAZ gene family DNA methylation Doenças Genéticas Determinantes da Saúde e da Doença Estados de Saúde e de Doença
Pedagogical Context
Citation
Hum Reprod. Epub 2010 Aug 4. doi:10.1093/humrep/deq200