• PMID: 15753313
• Gene Name: DNMT3L
• Condition: Required for spermatogenesis
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Required for spermatogenesis

Meiotic and epigenetic defects in Dnmt3L-knockout mouse spermatogenesis

Webster KE, O'Bryan MK, Fletcher S, Crewther PE, Aapola U, Craig J, Harrison DK, Aung H, Phutikanit N, Lyle R, Meachem SJ, Antonarakis SE, de Kretser DM, Hedger MP, Peterson P, Carroll BJ, Scott HS.

The production of mature germ cells capable of generating totipotent zygotes is a highly specialized and sexually dimorphic process. The transition from diploid primordial germ cell to haploid spermatozoa requires genome-wide reprogramming of DNA methylation, stage- and testis-specific gene expression, mitotic and meiotic division, and the histone-protamine transition, all requiring unique epigenetic control. Dnmt3L, a DNA methyltransferase regulator, is expressed during gametogenesis, and its deletion results in sterility. We found that during spermatogenesis, Dnmt3L contributes to the acquisition of DNA methylation at paternally imprinted regions, unique nonpericentric heterochromatic sequences, and interspersed repeats, including autonomous transposable elements. We observed retrotransposition of an LTR-ERV1 element in the DNA from Dnmt3L-/- germ cells, presumably as a result of hypomethylation. Later in development, in Dnmt3L-/- meiotic spermatocytes, we detected abnormalities in the status of biochemical markers of heterochromatin, implying aberrant chromatin packaging. Coincidentally, homologous chromosomes fail to align and form synaptonemal complexes, spermatogenesis arrests, and spermatocytes are lost by apoptosis and sloughing. Because Dnmt3L expression is restricted to gonocytes, the presence of defects in later stages reveals a mechanism whereby early genome reprogramming is linked inextricably to changes in chromatin structure required for completion of spermatogenesis. FAU - Webster, Kylie E AU - Webster KE AD - Genetics and Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia. FAU - O'Bryan, Moira K AU - O'Bryan MK FAU - Fletcher, Stephen AU - Fletcher S FAU - Crewther, Pauline E AU - Crewther PE FAU - Aapola, Ulla AU - Aapola U FAU - Craig, Jeff AU - Craig J FAU - Harrison, Dion K AU - Harrison DK FAU - Aung, Hnin AU - Aung H FAU - Phutikanit, Nawapen AU - Phutikanit N FAU - Lyle, Robert AU - Lyle R FAU - Meachem, Sarah J AU - Meachem SJ FAU - Antonarakis, Stylianos E AU - Antonarakis SE FAU - de Kretser, David M AU - de Kretser DM FAU - Hedger, Mark P AU - Hedger MP FAU - Peterson, Pärt AU - Peterson P FAU - Carroll, Bernard J AU - Carroll BJ