• PMID: 20685756
• Gene Name: DAZ1
• Condition: Oligoasthenoteratozoospermic (OAT)
• Association: DNA methylation pattern of the DAZ and DAZL promoter CGIs in quality-fractioned sperm populations from men with normozoospermia (NZ) and oligoasthenoteratozoospermia (OAT). This represents the ?rst time that the epigenetic state of these two key gametogen
• Population size: 20
• Population details: 15 men undergoing spermiogram analyses for infertility, 5 men selected with OAT, 5 controls
• Age: Control : 39.2+7.3 y, OAT: 39.4+7.2
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Oligoasthenoteratozoospermic

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

Navarro-Costa P, Nogueira P, Carvalho M, Leal F, Cordeiro I, Calhaz-Jorge C, Gonçalves J, Plancha CE.

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. FAU - Navarro-Costa, Paulo AU - Navarro-Costa P AD - Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal. navarro-costa@fm.ul.pt FAU - Nogueira, Paulo AU - Nogueira P FAU - Carvalho, Marta AU - Carvalho M FAU - Leal, Fernanda AU - Leal F FAU - Cordeiro, Isabel AU - Cordeiro I FAU - Calhaz-Jorge, Carlos AU - Calhaz-Jorge C FAU - Gonçalves, João AU - Gonçalves J