Figure 1: Proposed cycle of cause and effect by which oxidative stress in the male germ line impacts upon the health and well-being of future generations. (1) A variety of primary factors can initiate oxidative stress in the male germ line including infection, age, obesity and exposure to a variety of adverse environmental influences. (2) This initial oxidative stress induces lipid peroxidation culminating in the production of lipid aldehydes such as 4HNE, which bind to proteins in the mitochondrial electron transport chain, stimulating the generation of reactive oxygen species (ROS). The latter stimulate yet more lipid peroxidation in a self-propagating cycle that culminates in apoptosis. (3) One of the most sensitive targets of oxidative stress is the DNA in the sperm nucleus, generating 8-hydroxy, 2'deoxyguanosine (8OHdG) base adducts. (4) The fi rst enzyme in the base excision repair pathway, 8-oxoguanine glycosylase 1 (OGG1), is present in spermatozoa and its activity creates abasic sites. The remainder of the DNA repair pathway is present in the oocyte. The oocyte has to repair the DNA damage brought into the zygote by the fertilizing spermatozoon before the initiation of S-phase for the fi rst mitotic division. (5) If the oocyte makes a mistake at this stage of DNA repair, it has the potential to create a mutation that will be represented in every cell in the body and could account for the range of pathologies seen in the offspring of fathers exhibiting high levels of oxidative DNA damage in their spermatozoa. Abbreviations: IVF, in vitro fertilization; ROS, reactive oxygen species.