Oxidative Stress

Sperm dysfunction is one of the leading causes of subfertility.

Despite much research, there is limited knowledge about the causes of sperm dysfunction. However, oxidative stress (OS) has been identified as one of the causes of abnormal sperm function. OS refers to the state in which free radicals overwhelm the body´s antioxidant capacity. An excess of ROS can have harmful effects on the tissues and organs. For normal male fertility, a fine balance between the generation of ROS and its removal is very important. Excess of ROS also has a negative impact on the pregnancy outcome as well as the assisted reproductive techniques. Moreover, excess ROS can damage DNA in spermatozoa, induce cell apoptosis, and cause lipid peroxidation, which leads to morphological abnormalities, decrease in fertility, and increase sperm membrane permeability. It is important to effectively detect the amount of ROS in a semen sample in order to better treat subfertile male patients.

Oxidative stress is implicated in the etiology of male infertility and sperm dysfunction resulting in induction of lipid peroxidation, abnormal sperm function, and increase in mitochondrial and nuclear DNA damage.

Evidence now suggests that reactive oxygen species (ROS) mediated damage to sperm (“oxidative stress”) is a significant contributing pathology in 30-80% of cases of male infertility. ROS produce infertility by two principal mechanisms. First, ROS damage the sperm membrane, which in turn reduces the sperm´s motility and ability to fuse with the oocyte (impaired fertilization). Second, ROS directly damage the sperm DNA, compromising the paternal genomic contribution to the embryo. While IVF-ICSI undoubtedly overcomes any oxidative impairment of fertilization, it has no therapeutic effect on the quality of the paternal genome. Therefore, the injection of sperm with oxidatively damaged DNA may result in impaired blastocyst development, an increased risk of miscarriage and the birth of a child with sub-optimal paternal genetic compliment, potentially leading to disease in later life.

What is Oxidative Stress?

Oxidative stress is defined as an imbalance between oxidation and reduction towards the oxidative status, which can potentially result in cellular or genetic damage. This condition is triggered by so-called reactive oxygen species (ROS), which are chemical intermediates deriving from oxygen, most of them having one or more unpaired electrons (radicals) causing electronic instability and therefore very short half-life times in the nanosecond (10-9 s) to millisecond range (10-3 ) with high reactivity of the molecules. Practically, these radicals react at the site of generation. The most relevant examples of ROS in Andrology are the hydroxyl radical (OH), superoxide anion (O2) and hydrogen peroxide (H2O2). On the other hand, one has to distinguish between ROS, which can be radicals, but need not to be always (exception : H202) and radicals. Radicals are any form of molecule exhibiting one or more unpaired electrons.

In an ejaculate, there are two major sources of ROS, namely, leukocytes and the male germ cells themselves. Leukocytes physiologically generate high amounts of ROS, since this process plays a major role in infections, inflammations and cellular defense mechanisms to kill pathogens. If activated, leukocyte ROS generation can be up to 1000-times higher than that of spermatozoa. In addition, ROS and oxidative stress in semen can also be caused by numerous other factors.  Among them are exogenous sources such as environmental pollution by heavy metals, or other chemical compounds, and even lifestyle factors such as obesity, smoking, alcohol consumption and certain medical conditions such as spinal cord injuries or varicoceles.

(References: Agarwal et al., Studies on Men´s Health and Fertility, Humana Press, 2012)