Fig. 5

Effects of tobacco smoking on sperm DNA methylation. Cigarette smoking is associated with alterations in the expression of DNMT1, at both the mRNA and protein levels. Smoking results in double-stranded DNA breaks, resulting in the recruitment of DNMT1 for repair, and the activation of DNA-binding proteins that protect DNA from de novo methylation. Moreover, hypoxia induced by cigarette smoke alters the availability of methyl groups during early embryonic development. Hypoxia upregulates HIF-1α-dependent MAT2a, which synthesises S-adenosylmethionine, a methyl donor for DNA methylation. Finally, tobacco smoke may also alter DNA methylation by differential expression and activity of DNA binding factors such as SP1, a transcription factor involved in early embryogenesis. Figure was adapted from Lee and Pausova [111] and created with Biorender.com