Oxidative stress and male infertility

Giannis Chrysanthopoulos, B.Sc., M.Sc., Molecular Biologist-Reproductive Biologist

Oxidative stress (OS) has been reported to play an important role in several causes of male infertility, including male genital tract infection/inflammation, varicocele and adverse lifestyle conditions associated with diseases such as obesity and diabetes. Oxidative stress is caused by an imbalance between reactive oxygen species (ROS) and the antioxidants produced naturally by the body.

Under normal conditions, ROS and antioxidants are in balance. Antioxidants neutralize excessive amounts of these free radicals and maintain homeostasis. However, under pathological conditions, in which the concentration of ROS is higher than that of antioxidants, oxidative stress is induced. The imbalance can occur in the form of oxidative (>1.34) or reductive stress (<0.01) where either ROS occur in higher concentration because they are not neutralized, or antioxidants inactivate more ROS than necessary for the normal balance of the organism. The factors that can lead to oxidative stress can be exogenous, such as various toxins, smoking, alcohol consumption, diet and radiation, and can also be endogenous, the most typical example being the presence of varicocele. The plasma membrane of spermatozoa has a high content of polyunsaturated fatty acids, making them very sensitive to lipid peroxidation. For this reason, oxidative stress is a major contributor to male infertility, as ROS are also crucial for some important physiological processes, such as sperm activation and thus fertilization capacity (capacitation).

A recent study reported that the presence of oxidative stress in sperm reduces fertilization rates and negatively affects the developmental potential of the embryo up to blastocyst stage, the probability of implantation and clinical pregnancy and live birth rates. Furthermore, it has been proven that increased oxidative stress directly affects other parameters, such as sperm motility. Also, in addition to lipid peroxidation, elevated ROS levels can cause, shortening of chromosome telomeres, epigenetic changes, microdeletions on the Y chromosome and activation of apoptosis, i.e., programmed cell death. The overproduction of ROS also leads to additional important and detrimental effects on the genetic integrity of sperm, including sperm DNA fragmentation (SDF).

Recent systematic reviews suggest that increased oxidative stress has been associated with a reduction in natural conception rates and in combination with the DNA fragmentation, clinical pregnancy rates can decrease from 24% to 3%.

Despite the long-standing association of oxidative stress with many pathological conditions, including male infertility, caused by increased ROS concentration, recent evidence suggests that ROS levels are also increased by reductive stress, due to the accumulation of reducing molecules. In particular, mechanisms such as guanidine oxidation following DNA fragmentation can be observed following reductive stress.

Ways of dealing with oxidative stress in sperm

Reducing the oxidative stress in cells is essential to maintain harmony in the body, in order to carry out normal cellular functions, such as cell proliferation. This can be achieved either by improving lifestyle or by antioxidant intake, but also by combination of the two.

Regarding lifestyle improvement, it has been proven that a significant positive effect is achieved by limiting smoking and alcohol consumption, avoiding exposure to various environmental toxic factors (chemicals, radiation) and avoiding systematic exposure of the genital organs to heat factors (sauna, jacuzzi, electric blankets, tight clothing). Also, increasing in physical activity, and increasing the intake of foods rich in antioxidants, such as vitamin C (papaya, strawberries, kiwi, broccoli and oranges), vitamin E (spinach, sunflower seeds, almonds, papaya), selenium (mushrooms, mustard seeds) and zinc (spinach, sesame and pumpkin seeds and oats) can prove beneficial in such cases.

In many cases, the restoration of redox homeostasis can be facilitated by the simultaneous intake of targeted antioxidant supplements. These supplements contain specific concentrations, based on scientific data, of various elements such as vitamin E and C, glutathione, coenzyme Q10, carotenoids, omega fatty acids, L-arginine and polyphenols. These elements have been shown to have a beneficial effect on both elimination of oxidative stress and on sperm parameters (concentration, motility, morphology), when they are affected by the imbalance of the redox potential.


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