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Please use this identifier to cite or link to this item: http://hdl.handle.net/10451/4849

Title: Incorrect DNA methylation of the DAZL promoter CpG island associates with defective human sperm
Authors: Navarro-Costa, Paulo
Nogueira, Paulo
Carvalho, Marta
Leal, Fernanda
Cordeiro, Isabel
Calhaz-Jorge, Carlos
Gonçalves, João
Plancha, Carlos E.
Keywords: Male infertility
Spermatogenesis
Epigenetics
DAZ gene family
DNA methylation
Issue Date: 2010
Publisher: European Society of Human Reproduction and Embryology
Citation: Human Reproduction, Vol.25, No.10 pp. 2647–2654, 2010
Abstract: 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.
Peer Reviewed: yes
URI: http://hdl.handle.net/10451/4849
http://humrep.oxfordjournals.org/content/25/10/2647.full
ISSN: 0268-1161
Appears in Collections:FM-IMP-Artigos em Revistas Internacionais

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