Influence of Cytokines on Sperm Membrane Properties

An adverse effect of proinflammatory cytokines on sperm membrane properties (e.g., lipid peroxidation) is one of the several mechanisms by which cytokines might interfere with sperm quality. A peroxidation of the membrane structures is considered to be the first measurable destructive effect of ROI overproduction, also connected with infectious inflammation, and due to the high content of polyunsaturated fatty acids (PUFAs) spermatozoa are particularly susceptible to this process. An attack of free radicals toward the sperm membrane lipids leads to irreversible changes in membrane fluidity, enhances its nonspecific permeability, and in turn may affect the capacitation and acrosomal reactions abrogating the ability of spermatozoa to penetrate an oocyte. Our knowledge has to be broadened by systematic studies of lipid peroxidation in which the influence of lipid peroxidation on the sperm function can be evaluated [128-132] ] Moreover, human semen consists of spermatozoa subpopulations, differing in the content of lipid membranes, which may determine the degree to which they are endangered to peroxidative damage [133-135]. The decrease in the PUFAs, observed in some subpopulations of ejaculated spermatozoa, may be the evidence of their previous oxidation and shedding of the products of lipid peroxidation to seminal plasma.

Many years ago, Buch et al. [111] for the first time reported the increase of the ROS production by human spermatozoa after their incubation with IL-1a, IL-1P, or TNF-a, the measurable effect of which was an increase in sperm membrane peroxidation, judged by the MDA levels. The relationship between the IL-6 or IL-8 concentrations and the intensity of sperm membrane lipid peroxidation in the semen was also suggested by other authors [106, 136]. Analysis of a wide panel of recombinant proinflammatory cytokines in pathological (observed in situ) concentrations revealed the influence of some cytokine combinations (applied together with leukocytes) on MDA levels in different spermatozoal fractions [88]. Taking into consideration that some authors [138] have documented an increase in lipid peroxidation after in vitro incubation of sperm with PMA-stimulated leukocytes which suggests a decrease in the biological value of sperm membranes in the environment of oxidative stress, it may be argued that interleukins do not act separately but in connection with other mediators of the inflammatory process which has been suggested previously [57, 95, 105, 115, 137]. It cannot be precluded that the increase of oxidative stress in leuko-cytospermia is modulated by the levels of some cytokines, and even more, during inflammatory conditions, produced by leukocytes ROI and proinflammatory cytok-ines cooperate with each other provoking a destructive effect on spermatozoa.

According to data presented in some papers, there are some differences in the rates of lipid peroxidation that are related to the sperm maturity and, presumably, sperm membrane structures [ 138-140] , Probably, the mediating role of leukocytes with respect to the harmful effects of secreted proinflammatory cytokines toward sperm membranes may depend on the type of sperm subpopulation [88],

Proinflammatory cytokines are characterized by their pleiotropic properties, and when they occur together they may act synergistically, additively, or antagonistically on the biological function of the target cell. This is confirmed by the synergis-tic effect in vitro in relation to the harmful influence of some proinflammatory cytokines on biological membranes [88]. In case of cytokines such as IL-6, IL-8, or IL-18, observations in the in vitro system appear to be complementary to evaluation of the male genital tract inflammation in vivo. The evidence of this can be high levels of IL-6, IL-8, or IL-18 observed in the seminal plasma of infertile men reported by many groups [71, 72, 74]. The extended high levels of these cytokines present during persistent infection/inflammation in the male genital tract may augment the peroxidation process and affect sperm function with a subsequent development of infertility. Many authors suggest that the measurement of IL-6, IL-8, and/or IL-18 concentration in the seminal plasma can be a sensitive marker of early diagnosis of infection/inflammation in the male genitourinary tract and a signal for fast intervention with an anti-inflammatory treatment [57, 71, 72, 76].

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