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Reactive Oxygen Species (ROS), Semen

The reactive oxygen species (ROS) test measures the oxidative stress that the spermatozoa may be exposed to. High levels of oxidative stress result in damage to sperm DNA, RNA, and telomeres and, therefore might provide a common underlying etiology of male infertility and recurrent pregnancy loss, in addition to congenital malformations.

ROS in semen are measured by chemiluminescence (luminol) according to WHO procedure.

More information

ROS includes many reactive molecules and free radicals derived from molecular oxygen, which damage DNA and RNA and oxidize proteins and lipids (lipid peroxidation). The most common ROS include superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (HO-), and singlet oxygen (1O2), all of which are more reactive than oxygen (O2) itself.

The physiological role of ROS in spermatozoa

Physiologically, ROS are considered regulators of several intracellular pathways, modulating the activation of different transcription factors. Several studies showed that higher ROS levels stimulate sperm capacitation and hyperactivation, acrosome reaction, motility and chemotaxis, and chromatin compaction in maturing spermatozoa. Furthermore, ROS can improve sperm capacity for binding to the zona pellucida, inducing sperm-oocyte fusion.

The pathological role of ROS in spermatozoa

Besides the physiological role of ROS, excessive ROS generation and oxidative stress seem to be associated with harmful effects on spermatozoa, resulting in morphological and dynamic cellular properties alterations and finally in lower fertilization ability.

An altered redox balance in the seminal fluid may display deleterious effects on sperm homeostasis, leading to male infertility. ROS-mediated sperm oxidation may induce cellular dysfunctions, affecting spermatozoa concentration, total number, and motility.

Spermatozoa are particularly susceptible to ROS-induced oxidation due to the presence, in their plasma membrane, of elevated levels of polyunsaturated fatty acids.

Lipid peroxidation is strictly associated with fluidity and permeability membrane alterations, inhibition of membrane-bound enzymes and receptors, and activation of the apoptotic cascade, supporting oxidative stress involvement in motility and morphology sperms abnormalities.

It is accepted that nucleic acids represent another crucial target of oxidative stress. Both nuclear and mitochondrial DNA are vulnerable to hydroxyl radical (OH.) attack, leading to the formation of several biomarkers of oxidative stress. OH. can react with guanine to produce 8-hydroxy-2′-deoxyguanosine (8-OH-G), an important marker of DNA oxidative damage, detectable in several biological samples.

The lack of adequate antioxidant systems makes spermatozoa highly susceptible to DNA oxidation. Sperm DNA oxidation is also due to the lack of complete DNA repair strategies in spermatozoa.

Several studies indicated that ROS generation is associated with DNA fragmentation and poor chromatin packaging, promoting apoptosis with relevant consequences on sperm count.

Main Sources of ROS

It is largely accepted that several exogenous factors may contribute to inflammation and redox status alterations, promoting male infertility. Environmental pollution, lifestyle factors such as smoke, alcohol, obesity, varicocele, bacterial and viral infections, microorganism mutations, or sexually transmitted disorders are actively involved

However, seminal fluid oxidative stress is mostly due to leukocytes, which produce 1.000 more times ROS than normal spermatozoa, and immature spermatozoa.

Leukocytospermia. Granulocytes and macrophages are the main cell types found in the ejaculate and are responsible for ROS generation.

Immature spermatozoa. When spermatogenesis is defective, alterations in cytoplasmic extrusion mechanisms are observed and spermatozoa are released with an excess of residual cytoplasm (cytoplasmic droplets). Immature spermatozoa are associated with higher ROS generation.

Mitochondria. Another potential ROS source in spermatozoa is represented by mitochondria. Different factors may alter the electron transport chain on the mitochondrial membrane, resulting in excessive ROS generation. Several reports indicate sperm mitochondrial dysfunction and oxidative stress as potential factors involved in asthenozoospermia.

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