Oxidative stress Major executioner in disease pathology role in sperm DNA damage and preventive strategies

Abstract

Oxidative stress (OS) has been implicated in a wide array of diseases such as neurodegenerative disorders, autoimmune diseases, complex lifestyle diseases and cancer. OS is caused by an imbalance in production of Reactive Oxygen Species (ROS) and antioxidant defenses in the cell which results in the damage of cellular components, inactivate essential metabolic enzymes and disrupt signal transduction pathways. OS induces peroxidative damage to the sperm plasma membrane, DNA fragmentation in sperm nuclear/mitochondrial genome and causes dysregulation in levels of mRNAs/transcripts. OS induced sperm DNA damage is associated with male infertility, recurrent pregnancy loss (RPL), congenital malformations and high frequency of childhood disorders. OS induced pathologies are caused by endogenous and exogenous factors, majority of which, are modifiable. Antioxidant supplementation could help in relieving OS, however, its long-term usage may disrupt the intricate oxidation-reduction balance and can lead to "Reductive Stress". Adoption of simple lifestyle interventions may relieve OS and can also aid in its management. This may improve overall quality of life (QOL) and can reduce prevalence of OS induced diseases.

Gossypin Sıçanlarda Böbrek İskemi- Reperfüzyon Hasarına Karşı Korur

“…It was shown that increased production in reactive oxygen species (ROS) caused by I/R activates leukocyte infiltration in the kidney, and these infiltrated-leukocytes synergistically produce more ROS and cytokines that directly lead to renal damage [6] . ROS also inactivate antioxidant enzymes [7,8] and cause increase in activated neutrophils and cytokines [9,10] and contributes to the activation of apoptotic genes [11,12] . I/R increases level of pro-inflammatory cytokines such as nuclear factor kappa B (NF-κB) which plays a role in the regulation of various genes involved in the acute phase inflammatory reaction [13] , tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and decreases level of anti-inflammatory cytokines such as interleukin-10 (IL-10) [14][15][16][17][18] .…”

Sperm DNA damage diagnostics: when and why

“…By virtue of its high polyunsaturated fatty acid and limited cytosolic content and thus a highly deficient antioxidant capacity, and a highly truncated DNA damage detection and repair mechanism, sperm are most vulnerable to DNA damage and is dependent on the oocyte for complete removal of damaged DNA and oxidized DNA adducts. But aged oocyte with aberrant, inefficient, imperfect repair may result in persistence of DNA lesions and mutagenic DNA bases post fertilization ( 7 ). Persistence of mutagenic bases and dysregulated sperm transcripts may result in genetic and epigenetic abnormalities in the offspring ( 1 , 7 ).…”

“…But aged oocyte with aberrant, inefficient, imperfect repair may result in persistence of DNA lesions and mutagenic DNA bases post fertilization ( 7 ). Persistence of mutagenic bases and dysregulated sperm transcripts may result in genetic and epigenetic abnormalities in the offspring ( 1 , 7 ).…”

“…It is especially important to quantify DNA damage from sperm after preparation (after density gradient centrifugation) as these would give the exact SDF levels in the sample being used for assisted conception ( 15 ). Also, regular monitoring is warranted when antioxidants to prevent reductive stress as it may disrupt redox sensitive reactions, capacitation, hyperactivation, signal transduction processes, and cellular homeostasis ( 7 ).…”

“…Post fertilization embryo development can be severely impaired not only by sperm DNA damage but also by dysregulated levels of sperm transcripts, shorter telomeres, and altered levels of miRNA and abortive transcripts from damaged genes ( 16 ). Bisht and Dada reported normalization of levels of dysregulated transcript following YBLI ( 7 ). Thirty to eighty percent of men with unexplained infertility have raised ROS levels, which affects sperm structural and functional integrity.…”