Leukocytes and oxidative stress: dilemma for sperm function and male fertility

Abstract

Spermatozoa are constantly exposed to the interphase between oxidation through high amounts of reactive oxygen species (ROS) and leukocytes, and reduction by means of scavengers and antioxidants. Considering the very special functions as being the only cells with such high polarization and exerting their functions outside the body, even in a different individual, the female genital tract, the membranes of these cells are chemically composed of an extraordinary high amount of polyunsaturated fatty acids. This in turn, renders them very susceptible to oxidative stress, which is defined as an imbalance between oxidation and reduction towards the oxidative status. As a result, ROS deriving from both leukocytes and the male germ cells themselves cause a process called 'lipid peroxidation' and other damages to the sperm cell. On the other hand, a certain limited amount of ROS is essential in order to trigger vital physiological reactions in cells, including capacitation or the acrosome reaction in sperm. The treatment of patients with antioxidants to compensate the oxidative status caused by oxidative stress is highly debated as uncontrolled antioxidative treatment might derail the system towards the reduced status, which is also unphysiological and can even induce cancer. This paradox is called the 'antioxidant paradox'. Therefore, a proper andrological diagnostic work-up, including the evaluation of ROS levels and the antioxidant capacity of the semen, has to be carried out beforehand, aimed at keeping the fine balance between oxidation and scavenging of vital amounts of ROS.

Figure 1

Schematic depiction of sperm functional parameters.

Figure 2

Oxidation forms of oxygen. If molecular oxygen, which is a diradical with two unpaired electrons, is reduced, it acquires four electrons and water (H₂O) is formed. The dashes around the oxygen (O) represent paired, the points represent unpaired electrons.

Figure 3

Fenton and Haber-Weiss reaction.

Figure 4

Chemistry of lipid peroxidation. (a) Initiation and propagation phases by radicals. In the initiation phase, the lipid radical is stabilized in different resonance structures by delocalization of the free electron. In the propagation phase, the lipid radical reacts with molecular oxygen to form a lipid peroxyl radical which propagates the reaction by means of a radical chain reaction. (b) In the termination phase, two lipid radicals react with one another to form a stable bond. Also, from lipid hydroperoxyl radicals, a variety of degradation products like malondialdehyde, 4-hydroxy-2-alkenals or 2-alkenals are formed. These end products are mutagenic and genotoxic.