Comparison of Sperm Methylome in Fertile and Infertile Boars Carriers of DNA Translocation

Balanced chromosome translocations is one important cause of reduced fertility for boars and is mostly explained by the production of genetically unbalanced gametes. It has been also hypothesized that balanced chromosomal translocations affect fertility through the induction of epigenetic modifications in germ cells that alter the expression of important genes for meiosis and spermatid differentiation. We previously found abnormal methylation in the GNAS imprinted locus in 2 boars carrying chromosomal translocations. We thus aim to explore the effects of chromosomal translocations on gamete epigenetics by looking at sperm DNA methylation using genome-wide approaches.

By combining Reduced Representation Bisulfite Sequencing and sequencing of immunoprecipitated methylated DNA we compared the sperm methylome of 3 fertile and 3 infertile boars (including 2 with chromosomal translocation). Using these two methodologies we detected the previously described abnormal methylated region on the GNAS locus but we finally identified few DMRs between infertile and fertile boars and none was located close to genes with known function in spermatogenesis.

We then analyzed more in detail the regions located at the vicinity of the translocation breakpoints. We observed a global downregulation of gene expression close to DNA breakpoints and a partial reactivation of genes located on the X chromosome but we do not observed a higher density of DMRs around the translocation breakpoints and none close to the breakpoints. Our results suggest that the Meiosis Silencing of Unsynapsed Chromatin observed in spermatocytes is not associated with local DNA hypermethylation while genes around the translocation breakpoints were downregulated.