As it has been previously indicated, five major factors determine the rate of lipid peroxidation in mammalian sperm: (1) membrane-bound PUFA content, (2) oxygen radical production, (3) partial pressure of oxygen (pO2) in the extracellular medium, (4) temperature in the extracellular medium, and (5) antioxidant defense mechanisms.

PUFA are the actual substrate for lipid peroxidation reactions. In a way, they are like a "flammable jacket" that covers the sperm cell. However, as previously indicated, PUFA play a key role in the regulation of membrane fluidity, which is of paramount importance in the maintenance sperm motility and the membrane fusion reactions that take place during the process of fertilization. Therefore, PUFA cell content must be carefully regulated. That is perhaps why during the process of sperm maturation DHA content in immature sperm is significantly reduced, with mature sperm just retaining a critical mass of DHA that will allow sperm to reach the site of fertilization and complete the process of fertilization.

Oxygen radical production, on the other hand, is like the spark that ignites this flammable jacket and initiates lipid peroxidation by abstraction of a hydrogen from the bis-allylic methylene group of sperm membrane-bound PUFA. Oxygen radical production is determined, for the most part, by the rate of oxidative phosphorylation in the mitochondria and by the pO2 in the extracellular medium. The higher the flow of electrons through the inner mitochondrial membrane and the higher the pO2 in the extracellular medium, the higher oxygen radical production. While immature sperm produce high levels of oxygen radicals, mature sperm isolated from the gradient pellet produce very low levels consistent with their physiological role in the process of sperm capacitation [43] .

Temperature, on the other hand, determines both oxygen radical production and the rate of reaction of oxygen radicals with membrane-bound PUFA. The activation energy of these reactions is lowered at higher temperatures. In fact, it has been shown that the rate of lipid peroxidation in mammalian spermatozoa increases exponentially above 37°C and decreases significantly at temperatures below 36°C [46]. This would favor storage of sperm in the epididymis, where the temperature is below 36°C.

Concerning antioxidant defense mechanisms, spermatozoa have developed through evolution a strategy to prevent and counteract the occurrence of lipid peroxidation. This strategy includes (1) the presence of antioxidant enzymes, including SOD and GPX which eliminate superoxide anion and hydrogen peroxide and hydroperoxides, respectively, (2) PLA2 which removes lipid peroxides from the sn-2 position of phospholipids, thus preventing and reducing the propagation reactions of lipid peroxidation in the sperm membrane, and (3) sperm's metabolic strategy. Concerning the latter, the preferential conversion of glucose to lactate under aerobic conditions through the Embden-Meyerhof pathway may be an important evolutionary feature of sperm, perhaps intended to minimize the accumulation of reducing equivalents in the mitochondria, thus reducing oxygen radical production by the mitochondria.

It is well known that sperm produce oxygen radicals, that the bulk of these radicals are produced by the mitochondria, and that oxygen radical-induced damage could result in loss of sperm motility, loss of acrosomal contents, and oxidative DNA damage [47-52]. Conversion of glucose to lactate under aerobic conditions would (1) decrease production of mitochondrial NADH and FADH-reducing equivalents by the Krebs cycle and (2) decrease electron flow in the inner mitochondrial membrane, thereby downregulating oxygen radical formation. This metabolic feature of sperm is especially important outside the protective environment of the epididymis where oxygen radical-induced damage is minimized by a lower temperature and lower pO2.

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.

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