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.

Cytosolic and mitochondrial ROS: which one is associated with poor chromatin remodeling?

“…They further stated that the concentration of vitamin C supplements is of importance because a high concentration of vitamin C could act as a reducing agent and interfere with the disulfide bonds between the protamines. Such paradoxes are called the 'antioxidant paradox' (reviewed in [Henkel 2011]). This study revealed a positive correlation between the percentage of cytoplasmic (DCF + sperm) and mitochondrial (R123+ sperm) ROS with sperm viability and motility.…”

Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

“…64 The presence of leukocytes on the sperm surface and the similarity of their cellular mechanisms for superoxide generation to those of activated spermatozoa could explain the decrease in superoxide anion generation in spermatozoa. 65,66 It is believed that leukocytes and spermatozoa share a similar mechanism for ROS generation: an NADPH oxidase located in or near the cell membrane. 67 Although controversy exists regarding the form of this enzyme, 68 exogenous gangliosides undeniably decrease the extracellular production of superoxide radicals.…”

Sperm surface changes and physiological consequences induced by sperm handling and storage

“…However, if achieving the correct balance between oxidation and reduction were so simple, then antioxidants would be routinely included in all semen diluents. The reason this does not occur is that uncontrolled antioxidant treatment can also be detrimental, as cells generally function in a reduced state (termed the 'anti-oxidant paradox'; reviewed by Henkel (2011)). For instance, capacitation is reduction dependent and it is not clear whether excessive anti-oxidant protection during sperm handling renders the surviving cells responsive to a capacitation-inducing environment.…”