Sensitivity of Spermatozoa to Oxidative Damage

Spermatozoa are very special cells. They are not only the smallest but also the most polarized cells in the body that fulfil their functions even outside the body in a different individual, the female genital tract. To maintain this extreme polarization, spermatozoa exhibit a specially composed plasma membrane containing an extraordinary amount of polyunsaturated fatty acids (PUFA) [46, 47]. This high PUFA content is essential for normal sperm function, as it is the foundation for the sperm plasma membrane's high fluidity [48]. In turn, membrane fluidity is directly related to normal sperm functions [47,49] which can actually be regarded as membrane functions [50, 51],

The total content of PUFA in human spermatozoa accounts for about 50% of the content of fatty acids. Docosahexaenoic acid (DHA), a PUFA containing six double bonds per molecule [46] is of particular importance as its content represents about 21.5% of the total fatty acid and 43.0% of the unsaturated fatty acid content of human spermatozoa (reviewed in [41]). The importance of the PUFA content of the sperm plasma membrane in infertile patients with oligozoospermia and/or astheno-zoospermia was debated, as contradictory data were presented by different groups. While Zalata et al. [46], Lenzi et al. [52] and Tavilani et al. [53] showed low PUFA levels in patients with poor sperm motility, Ollero et al. [54] as well as Khosrowbeygi and Zarghami [55] observed higher PUFA concentrations, especially DHA, in patients with poor sperm motility than in normozoospermic samples. Apparently, this obvious discrepancy is due to aberrant transformation of defective germ cells during their morphogenesis leaving these cells with too high PUFA levels triggering mitochondrial ROS production and causing oxidative stress [56]. The aforementioned discrepancies are interpreted by these authors as result of different end points used in the different studies.

Furthermore, spermatozoa are characterized by their very special morphological features, which comprise not only the extreme polarization but also the dramatic loss of most of the cytoplasm during spermatogenesis. As a result, the male germ cells exhibit an inevitable lack of intrinsic antioxidative protection by ROS scavengers such as catalase, glutathione peroxidase (GPx) or superoxide dismutase (SOD) as well as non-enzymatic molecules such as vitamin C, vitamin E or glutathione. Both these factors, the intrinsic lack of antioxidant protection together with the extraordinary high content of PUFA in the plasma membrane, make the male germ cell extremely vulnerable to oxidative stress. Since developing spermatozoa have a very limited ability to DNA repair, replenishment and regeneration of glutathione, this oxidative stress does lead not only to disturbed sperm functions but also to damaged DNA [57],

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