Balance Between Oxidation and Reduction

On the one hand, ROS and oxidative stress are detrimental to spermatozoa and sperm functions because of the very special membrane lipid composition of the male germ cells. On the other hand, however, ground-breaking studies by de Lamirande and Gagnon [178, 179] show that superoxide not only is detrimental to sperm but also plays an essential role in triggering cellular events such as capacitation and hyperactivation, which are crucial requirements for sperm zona pellucida penetration [180]. Aitken et al. [181,182] as well as Griveau and Le Lannou [183] confirmed this function of ROS. Moreover, it could be shown that besides capacitation and hyperac-tivation, acrosome reaction, sperm zona binding and oocyte fusion are also stimulated by various low levels of ROS even in other species [43, 50, 184],

Conversely, high levels of activated, ROS-producing leukocytes are without question harmful to sperm functions and male fertility. Nevertheless, this detrimental effect of oxidative stress is also depending on the TAC of the ejaculate. Thus, it is not enough to determine only one parameter, either seminal ROS or TAC. Therefore, a combination of both parameters as a ROS-TAC score as proposed by Sharma et al. [185] appears to be superior to ROS or TAC in discriminating between fertile and infertile men. This suggestion seems reasonable because the balance between oxidants (ROS) and antioxidants (TAC) is essential for normal sperm function.

Since the ROS-TAC score decreases as oxidative stress increases caused by leukocytes, it is difficult, if not impossible, to determine a proper cut-off for leukocyte contamination [32, 186], For instance, a patient's fertility might not be compromised even if high numbers of non-activated leukocytes producing only small amounts of ROS are present in his ejaculate if this patient shows high seminal levels of TAC at the same time. In contrast, another patient might have compromised anti-oxidative seminal protection with low numbers of activated leukocytes, which produce high ROS levels. Because of this, the latter patient might be infertile. This example shows that the system of seminal oxidants and antioxidants as a whole has to be finely balanced in order to function properly [41]. Essentially, spermatozoa have to "walk a tightrope" and they will not be functionally competent, if the system of oxidants and antioxidants as a whole deviates to either side; it has to be finely balanced in order to function properly. Therefore, to be on the safe side in a clinical set-up, the presence of seminal leukocytes should rather be lower than higher and the cut-off for leukocytospermia of 1 x 106 leukocytes/mL as recommended by the WHO [28], should be lowered as previously suggested [32-34] .

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