الفهرس 
MALE REPRODUCTIVE PHYSIOLOGYOnly 14 pages are availabe for public view
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Abstract
I
nfertility is defined as one year of unprotected intercourse without conception. Approximately 25% of sexually active couples without contraception do not conceive within one year. On evaluation, roughly 50% of affected couples have causal or associated male factors as a cause of infertility.
Cells living under aerobic conditions constantly face the oxygen (O2) paradox. O2 is required to support life, but its metabolites such as reactive oxygen species (ROS) can modify cell functions, endanger cell survival or both. Hence, ROS must be continuously inactivated to keep only a small amount necessary to maintain normal cell function.
Generally, the term oxidative stress (OS) is applied when oxidants outnumber antioxidants, when peroxidation products develop, and when these phenomena cause pathological effects. Excessive ROS production that exceeds critical levels can overwhelm antioxidant defense strategies of spermatozoa and seminal plasma, causing OS. High levels of ROS are detected in semen samples of 25% to 40% of infertile men.
Spermatozoa are particularly susceptible to OS-induced damage because their plasma membranes contain large quantities of polyunsaturated fatty acids (PUFA) that susceptible for lipid peroxidation and their cytoplasm contains low concentrations of enzymes that scavenge ROS.
Levels of ROS can be measured in washed sperm suspensions using chemiluminescence assay employing probes such as luminol or lucigenin. Total antioxidant capacity (TAC) in the seminal plasma can be measured using an enhanced chemiluminescence assay.
ROS-TAC score considers as a new method for assessment of OS status in infertile men. The new ROS-TAC score is a statistical formula derived from measuring levels of ROS in washed sperm suspensions and TAC in seminal plasma. The score is an accurate measure of seminal OS, and low scores indicate high seminal OS.A value of 30 was determined as the lower limit of the normal range for the score, and individuals with scores below this cutoff value were found to be at particular risk for prolonged inability to initiate pregnancies.
There are multiple dangerous effects of increased ROS and oxidative stress on spermatozoa as:
1- The increased formation of ROS has been correlated with a reduction of sperm motility. The link between ROS and reduced motility may be due to a cascade of events that result in a decrease in axonemal protein phosphorylation and sperm immobilization, both of which are associated with a reduction in membrane fluidity that is necessary for sperm-oocyte fusion.
2- Oxidative stress has also been correlated with high frequencies of single and double DNA strand breaks. Strong evidence suggests that high levels of ROS mediate the DNA fragmentation commonly observed in spermatozoa of infertile men.
3- High levels of ROS disrupt the inner and outer mitochondrial membranes. This results in the release of cytochrome-C protein from the mitochondria that induce apoptosis.
Normally, antioxidant scavengers constantly inactivate ROS. Seminal fluid contains significant amounts of antioxidants. The human body uses three general systems of antioxidants: endogenous antioxidants, dietary antioxidants, and metal-binding proteins.
The dosage of the antioxidant appears to be very critical. It is of importance to note that ROS are also required for important physiological purposes. So excessive antioxidants may cause impaired sperm function by inhibiting ROS.
Vitamin E: was found to be effective in vitro in dose (10 mmol/l) and in vivo in dose (300 mg twice/day for 2 months). It reduces lipid peroxidation, improves sperm motility and pregnancy rate.
Vitamin C: was found to be effective in vitro in dose (100-200 micromol/l) and in vivo in dose (1000 mg/day). It reduces lipid peroxidation, improves sperm concentration, morphology and viability.
Glutathione (GSH): was found to be effective in vitro in dose (10 mmol/l) and in vivo in dose (400-600 mg/day for 2 month). It reduces lipid peroxidation, decreases DNA damage and increases sperm concentration and motility.
N-Acetyl-L cystine (NAC): was found to be effective in vitro in dose (0.1-10 mmol/l) and in vivo in dose (600mg/day). It decreases DNA damage and improves sperm concentration, morphology and motility.
Pentoxifylline: was found to be effective in vitro in dose (10mmol/l) and in vivo in dose (1200 mg/day). It reduces lipid peroxidation and increases sperm motility.