Inflammatory Conditions in the Gonad Oxidative Stress

The oxidative stress and lipid peroxidation, which occur in the gonad, are significant factors responsible for male infertility arising from the imbalance between production of reactive forms of oxygen and the efficiency of systems which eliminate

Oxidative Stress And Female Infertility

Exogenous antioxidants: polyphenols, vitamin C, vitamin E and carotenoids

Fig. 9.3 Oxidative stress as a link between inflammation and apoptosis. The inflammatory state induces activation of macrophages and release of cytokines leading to free radicals (ROS). ROS leads to damage of plasma membranes, DNA, and other cell structures. Inflammation causes transfer of NF-kB to cell nucleus and trigger transcription of "death genes" and apoptosis or pro-proliferative genes (cytokines)

Exogenous antioxidants: polyphenols, vitamin C, vitamin E and carotenoids

Fig. 9.3 Oxidative stress as a link between inflammation and apoptosis. The inflammatory state induces activation of macrophages and release of cytokines leading to free radicals (ROS). ROS leads to damage of plasma membranes, DNA, and other cell structures. Inflammation causes transfer of NF-kB to cell nucleus and trigger transcription of "death genes" and apoptosis or pro-proliferative genes (cytokines)

their harmful influence. To a group of oxygen radicals belong superoxide anion radical, hydroxyl radical, nitrogen oxide, and peroxide nitrite. ROS are formed as a by-product of the mitochondrial and microsomal electron transport as well as through the influence of cytochrome P450 enzymes on cholesterol and its metabolites. They are highly reactive compounds and may react with proteins, lipids, and DNA causing their damage which is prevented by the enzymatic antioxidative system, mainly superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx). However, in inflammation, the antioxidative protection is insufficient compared with the amount of radicals produced and this causes greater damage to the cell structures [38, 39] (Fig. 9.3).

Oxidative stress arises, among others, due to the exposure of the gonads to toxins, chemotherapy, ionizing radiation, bacterial inflammation, cryptorchidism, or pathology of veins in the spermatic cord (varicocele) [39] . The Leydig cells are physiologically and sometimes physically connected with macrophages, which makes possible their direct exposure to the growth factors and/or differentiation factors which are secreted by macrophages. It was shown that in physiological conditions macrophages produce and secrete 25-hydroxycholesterol which stimulates the Leydig cells to produce testosterone [40, 41] . In inflammatory conditions, however, macrophages are activated by, e.g., LPS and produce proinflammatory cytokines, such as IL-1 or TNF-a and also ROS. Therefore, beginning of the inflammatory reaction may have an influence on spermatogenesis through inhibition of steroidogenesis. LPS conditions determine an increase in the NO production by endothelial nitric oxide synthase (eNOS) in the endoepithelial cells and induce iNOS expression in macrophages. The increase in the NO concentration influences steroidogen-esis in the Leydig cells in vivo; however, this mechanism has yet to be studied and has not been well recognized [41, 42].

The StAR protein takes part in the binding and transport of cholesterol to the mitochondrial matrix and, thus, steroid production. These processes depend on the mitochondrial electrochemical gradient.

Studies on MA-10 tumor Leydig cells showed that ROS may cause disturbances of the mitochondrial electrochemical gradient, and through this inhibition of cholesterol import by StAR and a decrease of the testosterone synthesis which lead to apoptosis of reproductive cells [43, 44].

The Sertoli cells protect seminiferous tubules against autoantigens and pathogens. Cytokines IL-1 and IL-6 are secreted under the influence of the inflammatory factor, such as LPS, which induces in vitro inflammatory conditions in the Sertoli cells [1,45,46], and ROS activity causes peroxidation of the cell membranes, which due to the high content of polyunsaturated fatty/lipid acids are susceptible to the influence of free radicals [45]. The Sertoli cells synthesize GSH, which is the source of amino acids in the process of spermatogenesis, and provides protection to sper-matogenic cells against ROS [47, 48]. Reactive forms of oxygen are the reason of peroxidative damage to the sperm, which may cause infertility. Apart from the influence on peroxidation of the cell membrane lipids, ROS cause damage to DNA and may lead to apoptosis through DNA fragmentation. A large number of all divisions to which reproductive cells in the seminiferous tubules are submitted to during sper-matogenesis expose their chromosomes to the harmful influence of ROS [48].

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

Get My Free Ebook


Post a comment