Meiotic and epigenetic aberrations inDnmt3L-deficient male germ cells

Abstract

The DNA methyltransferase‐like protein Dnmt3L is necessary for the establishment of genomic imprints in oogenesis and for normal spermatogenesis (Bourc'his et al., 2001; Hata et al., 2002). Also, a paternally imprinted gene, H19, loses DNA methylation in Dnmt3L^−/− spermatogonia (Bourc'his and Bestor, 2004; Kaneda et al., 2004). To determine the reason for the impaired spermatogenesis in the Dnmt3L^−/− testes, we have carried out a series of histological and molecular studies. We show here that Dnmt3L^−/− germ cells were arrested and died around the early meiotic stage. A microarray‐based gene expression‐profiling analysis revealed that various gonad‐specific and/or sex‐chromosome‐linked genes were downregulated in the Dnmt3L^−/− testes. In contrast, expression of retrovirus‐like intracisternal A‐particle (IAP) sequences was upregulated; consistent with this observation, a specific IAP copy showed complete loss of DNA methylation. These findings indicate that Dnmt3L regulates germ cell‐specific gene expression and IAP suppression, which are critical for male germ cell proliferation and meiosis. Mol. Reprod. Dev.