Oxidative stress and male infertility

Male fertility highly depends on a biochemical pathway, called spermatogenesis. Through this process millions of spermatozoa are produced by the testicles. There is a large variety of factors which can affect this pathway, causing a negative impact on the quantity and quality of the sperm cells produced. One of those factors is known as Oxidative Stress (OS) and has been characterized as one of the main reasons of male infertility, affecting 30-80% of infertile men. OS is observed when the defensive, anti-oxidant system of the human body fails to neutralize the excessive production of Reactive Oxygen Species (ROS). Although low concentrations of these molecules are vital for the normal function of the male reproductive system and the processes which take place in it, increased concentrations may alter the structure of proteins and enzymes, damage the integrity of sperm DNA, leading to reduced fertilisation. It is of great importance to highlight that spermatozoa bearing extended DNA damage may have the potential to fertilise an oocyte, however, as a pregnancy progresses the paternal genome may disturb the normal embryo development which may lead to a pregnancy loss.

Under normal conditions, low amounts of ROS are produced by the thousands of mitochondria which are located on the middle piece (“neck”) of spermatozoa. These small amounts of ROS are essential for capacitation, hyperactivation, motility and, consequently, fertilization. The male reproductive system, mainly through the seminal plasma, has developed its own antioxidant defense to protect itself from the detrimental effects of excessive ROS concentrations. Vitamin C, Vitamin E, β-carotenoids (rich in carrots, sweet potatoes, and other vegetables), albumin, and selenium are just some of the antioxidant molecules found in seminal plasma and are of vital importance as they minimize the ROS formation reducing in turn the oxidative stress, cell death, and sperm DNA fragmentation rates.

What can cause, however, the excessive production of ROS?

• Leukocytes (also called White Blood Cells, are cells made in the bone marrow as key part of the body’s immune system; commonly found in circulation), which are present in almost any ejaculate, have been named as the main source of ROS in pathological conditions. Studies have showed that leukocytes produce at least 1000 times more ROS compared to spermatozoa. Leukocytes concentrations may significantly increase in ejaculates after a virus or bacterial infection of the male reproductive system.
• Spermatozoa bearing abnormalities (abnormal heads, “neck” abnormalities, tail defects etc.) have also been found to contribute to increased ROS generation in semen. For instance, men dealing with teratozoospermia have higher amounts of ROS in their ejaculates compared to proven fertile men justifying their sub-fertile or even infertile status.
• Smoking, among other detrimental effects, increases leukocyte concentration via inflammation reaction leading to leukocyte-derived ROS generation, which is positively correlated with the spermatozoa’s own intrinsic ROS production.
• Alcohol consumption can intervene with biochemical pathways taking place in mitochondria, increasing ROS concentration in semen and the rate of morphological or DNA abnormalities in spermatozoa.
• Exposure to environmental pollutants (phalate esters, NO, Pb, radiation) may increase ROS production impairing spermatogenesis procedure.
• psychological stress and intense physical exercise also increase the levels of ROS in seminal plasma leading to the reduction in sperm quality.
• Men dealing with obesity, varicocele or diabetes have increased chances of high ROS concentrations in their ejaculates and, hence, facing fertility problems. Obese men, for example, suffer from high metabolic rates leading to ROS overproduction which, accompanied with the increased temperature in testicles, can cause denaturation of enzymes and proteins vital for the normal completion of spermatogenesis.
• Studies have also shown a positive correlation between age, ROS generation, and sperm DNA fragmentation rate.

Therefore, the increase in oxidative stress, is highly dependent on lifestyle. Still, there are no specific guidelines from the World Health Organization (WHO) addressing the need for routine evaluation of OS in men. Nowadays, however, there are several commercially available oxidative stress diagnostic techniques, which may be utilized as an extra test to the basic parameters of a typical semen analysis (sperm motility, concentration and percentage of normal forms) and provide a thorough assessment of male fertility status.

There is no general consensus regarding the management of oxidative stress. As new diagnostic techniques become available and new treatments are proposed to tackle this problem, every man who cares about his fertility should improve his lifestyle (nutrition, exercise, restriction of alcohol and nicotine consumption), and speak to an expert if he has reasons to worry. The scientific team of Newlife IVF Greece is always up to date with the latest technologies available and will be more than happy to meet you and provide any extra information you might need to know.