Oxidative Stress and Its Outcomes Related to Male Infertility, Evidences For Genetic And Epigenetic Interactions

Male infertility is a multifactorial disorder involving a wide range of factors, including inflammation, infection, genetic, epigenetic, environmental and lifestyle-related factors. According to several studies all these factors are involved to produce high levels of reactive oxygen species (ROS) in the male genital system named as oxidative stress (OS). Indeed, the OS is a condition, which basically represents an imbalance between the systemic ROS generation and a biological system s ability to readily detoxify (antioxidant defenses) the reactive intermediates and/or to repair the resulting damage. The OS is able to negatively affect the spermatogenesis as well as sperm cell series via different mechanism affecting their DNA, RNA, lipid and protein contents. For instance, the OS is able to potentially affect the cellular mitochondria membrane and DNA content, leading to severe impairments in germ cell metabolism ratio, mitochondria-dependent apoptosis at both germ cell and sperm levels and hypospermatogenesis ormaturation arrest via suppressing ATP production in progressing germ cells during spermatogenesis. Moreover, the DNA content of mitochondria is not protected with histones and has a very limited capacity for DNA repair. Thus, considering that, the sperms contain large numbers of mitochondria, any mitochondrial damages (produced by OS), apart from its effect on sperm DNA damage, results in considerable loss of sperm motility. As another adverse effect of OS in male infertility problems, the oxidative DNAdamage (ODD) is able to potentially impair the germ and sperm cells epigenetic via defecting DNA methylation pattern and results in global hypomethylation and genomic instability, which finally is able to end with male infertility. Moreover, the OS-induced changes in histoneprotamine replacement and/or impaired histone acethylation pattern, simultaneous with OS on the genital system, negatively affects the spermatogenesis, and results in severe DNA damage, and predispose to Sertoli-cell-onlysyndrome or testicular cancers. Moreover, the elevated ROS levels imbalances the calcium signalling pathways, protein phosphorylation and various protein-kinase signalling processes. Thus, it could be concluded that, the OS is able to widely and fairly impact the molecular signaling networks of germ and sperm cells via negativelyaffecting their nucleotide and protein backbones.

کلیدواژه ها:

Infertility ، Oxidative stress ، Epigenetic ، DNA damage ، Mitochondria failure