*1.3.1 Lipid peroxidation of plasma membrane*

Lipids are present in spermatozoa plasma membrane in the form of polyunsaturated fatty acids (PUFA), most susceptible to oxidative damage [13, 14]. Once there is generation of lipid peroxide radical, it will react with the neighboring lipid molecule, triggering a chain reaction that can lead to >50% oxidation of the spermatozoa plasma membrane [15]. Byproducts of lipid oxidization include mutagenic and genotoxic molecules malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), leading indirectly to DNA damage [16]. Buffalo spermatozoa are more prone to oxidative damage than that of cattle, since it is rich in polyunsaturated fatty acids like arachidonic acids and docosahexaenoic acids [17].

**75**

*Effects of Oxidative Stress on Spermatozoa and Male Infertility*

Free radicals have the capability to directly damage spermatozoa DNA via single- and double-strand DNA breaks, cross-links and chromosomal rearrangements [18, 19]. ROS also can cause various types of gene mutations such as point mutations and polymorphism, resulting in decreased semen quality [20]. Other mechanisms such as denaturation and DNA base-pair oxidation also may be involved. Although most of the spermatozoa genome (85%) is bound to central nucleoprotamines that protect it from free radical attack [21], infertile men often have deficient protamination, which may make their sperm DNA more vulnerable to ROS damage [22]. A common byproduct of DNA oxidation, 8-hydroxy-2-deoxyguanosine (8-OH-2- deoxyguianosine), has been considered a key biomarker of

Decreased motility has been shown to be due to ROS-induced peroxidation of lipids in the spermatozoa membrane decreasing flexibility and by inhibition of motility mechanisms [24, 25]. The axosome and associated dense fibers of the middle pieces in spermatozoa are covered by mitochondria that generate energy from intracellular stores of ATP. It is well established that ROS can induce axonemal and mitochondrial damage, resulting in the immobilization of spermatozoa [26, 27]. In addition, ROS-induced damage of mitochondrial DNA leads to decreased ATP and energy availability and leads to activation of caspases and ultimately apoptosis, impeding spermatozoa motility [28, 29]. H2O2 can diffuse across the membranes of spermatozoa and inhibit the activity of some vital enzymes such as glucose-6-phosphate dehydrogenase (G6PD), which is an enzyme controlling the intracellular availability of NADPH. This is used as a source of electrons by spermatozoa to fuel the generation of ROS by an enzyme system known as NADPH oxidase [30]. Another hypothesis involves a series of interrelated events resulting in a ROS-reduced motility due to a decrease in axonemal protein phosphorylation and mitochondrial membrane damage and leakage of intracellular enzymes [31]. Meanwhile, cytochrome c release during the apoptotic pathway further increases levels of ROS, promoting DNA damage and fragmentation [32]. Especially after frozen–thawed cycles, spermatozoa with higher levels of oxidative stress have higher levels of caspase activation that can

High levels of ROS disrupt the mitochondrial membranes, inducing the release of the cytochrome c protein and Ca2+ and activating the caspase-inducing apoptosis [34]. Apoptosis in spermatozoa also may be initiated by ROS-independent pathways involving the cell surface protein Fas, which is a type I membrane protein that belongs to the tumor necrosis factor-nerve growth factor receptor family and mediates apoptosis [35]. Mitochondrial exposure to ROS also results in the release of apoptosis-inducing factor (AIF), which directly interacts with the DNA to cause

Lipid peroxides and DNA damage are the most typical oxidative stress injury

in sperm. Lipid peroxides are spontaneously generated in the sperm plasma

*DOI: http://dx.doi.org/10.5772/intechopen.86585*

this oxidative DNA damage [23].

*1.3.2 DNA damage*

*1.3.3 Motility*

trigger apoptosis [33].

DNA fragmentation in spermatozoa [36, 37].

*1.3.5 Fertilization, pregnancy and miscarriage*

*1.3.4 Apoptosis*
