Damage to Sperm DNA Mediated by Reactive Oxygen Species: Its Impact on Human Reproduction and the Health Trajectory of Offspring

Abstract

Disruptions to the genetic integrity of the mammalian spermatozoon play a major role in determining the subsequent developmental trajectory of the embryo. This chapter examines the causative links that connect DNA damage in human spermatozoa and the appearance of mutations in the progeny responsible for a variety of clinical conditions from autism to cancer. Integral to this discussion is an abundance of evidence indicating that human spermatozoa are vulnerable to free radical attack and the generation of oxidative DNA damage. The resolution of this damage appears to be initiated by the spermatozoa but is driven to completion by the oocyte in a round of DNA repair that follows fertilization. The persistence of unresolved oxidative DNA damage following zygote formation has the potential to create mutations/epimutations in the offspring that may have a profound impact on the health of the progeny. It is proposed that the creation of oxidative stress in the male germ line is a consequence of a wide variety of environmental/lifestyle factors that influence the health and well-being of the offspring as a consequence of mutational change induced by the aberrant repair of oxidative DNA damage in the zygote. Factors such as paternal age, subfertility, smoking, obesity, and exposure to a range of environmental influences, including radio-frequency electromagnetic radiation and xenobiotics, have all been implicated in this process. Identifying the contributors to oxidative stress in the germ line and resolving the mechanisms by which such stressors influence the mutational load carried by the progeny will be an important task for the future. This task is particularly pressing, given the extensive use of assisted reproductive technologies to achieve pregnancies in vitro that would have been prevented in vivo by the complex array of mechanisms that nature has put in place to ensure that only the fittest gametes participate in the generative process.

Urinary phthalate and phthalate alternative metabolites and isoprostane among couples undergoing fertility treatment

“…The direct mechanisms by which phthalates may induce these adverse reproductive outcomes are not clear but there is growing evidence that oxidative stress may be a contributing factor. Oxidative stress is implicated in adverse reproductive conditions including sperm DNA damage (Gavriliouk and Aitken, 2015), endometriosis (Mier-Cabrera et al, 2011; Sharma et al, 2010), and polycystic ovary syndrome (Palacio et al, 2006). Additionally, recent evidence suggests strong positive associations between urinary phthalate metabolite concentrations and biomarkers of oxidative stress among pregnant women (Ferguson et al, 2014; Ferguson et al, 2015; Holland et al, 2016), couples who were planning pregnancy (Guo et al, 2014), and the general US population (Ferguson et al, 2012).…”

Glutathione antioxidant protection system in ejaculated spermatozoa of infertile men with different forms of pathospermia

“…In particular, it was shown [9] that ROS produced by white blood cells, cause damage of sperm DNA. Although the presence of leukocytes in semen did not diminish the in vitro fertilizing capacity of spermatozoa, the introduction of leukocytes into washed spermpreparationsreducedspermfunctionbyROSproduction [2].Thisfindingseems paradoxic,butitindicatesthatseminalplasmahassignificantantioxidantorROSsca venging capacity which may prevent sperm damage by the leukocytes.…”

Role of environmental and genetic factors in autism spectrum disorder

“…Thus, paternal aging was known to be linked with several adverse clinical conditions including ASD. 42 The study of Lampi et al supports premature birth as a significant risk factor for ASD. 25 In Bangladesh around 13 to 25% babies are reported to born preterm, 44, 45 which is quite high and supports our finding that neurodevelopmental disorder may arise from preterm birth leading ASD.…”

“…15 Croen et al found that risk of ASD was increased significantly with each 10 years increase in maternal and paternal age. 14 According to some researchers, the father aged over 35 years 42 and mother aged over 30 or 35 years 1, 21 were suspected as a high-risk condition. This delaying childbearing trend contributes around 4.6% increase in autism over the decade.…”