**3. Effect of cadmium (Cd) on tyrosine phosphorylation**

Cd possesses oxidation state +2 just like mercury and calcium with half-life of 15–30 years with low execration rate. It can accumulate into the non-smoking population via fumes, dust, contaminated food and water and it is widely use in cancer drugs [98, 99]. Tobacco plant absorbs Cd specially into leaves which is then used in smoking [100]. Apart from this 0.5 mg of Cd is radially reported into per kg fertilizer which is then accumulate into the fruits, vegetables and grains [101, 102]. Cd is reported to accumulate in various tissues via bloodstream [103]. Ca shows a high affinity toward sulfhydryl (–SH and GHS) and disulphide groups (-S-S) of the proteins and result in increased production of ROS [104]. Epigenetic changes like DNA methylation are reported to associated with the in-vivo Cd exposure in three-month-old rats. Short time exposure of Cd for 24 h–1 week induces hypomethylation, while longer times (8–10 weeks) induce hypermethylation [105]. In-vivo orally administered Cd (1, 2 or 4mg kg−1) to 3–7-days postpartum rats for 30 min did not showed any effect on sperm motility, but significantly decrease the rate of fertilization and embryo development indicating that Cd affects the epigenetic factors [106, 107]. Cd is also reported to induced germ cell apoptosis, loss of daily sperm production, and decreased sperm motility might be responsible for the decline of male fertility [108, 109] specifically spontaneous acrosome reaction in mouse [109–111], rats [112], ram [113], rabbit [114] and sheep [115, 116] sperms. Research indicates that oxidative stress and apoptosis are the major players which affects the in the post-translation modifications like phosphorylation and methylation [117, 118]. Ca2+/calmodulin-dependent kinase II (CaMK-II) which is sensitive to concentration of intracellular calcium and calmodulin, are involve in apoptotic pathway [119–121] and responsible for phosphorylation of serine/thrionine residue of tyrosine kinase [119]. Wang et al. [122] reported that 10 μM Cd inhibited

#### *Effect of Heavy Metals on Tyrosine Kinases Signaling during Sperm Capacitation DOI: http://dx.doi.org/10.5772/intechopen.99261*

the sperm motility, GAPDH activity, AMPK activity and ATP production, and induced tyrosine phosphorylation of 55–57KDa proteins. These results suggest that Cd-induced tyrosine phosphorylation of 55–57KDa proteins particularly localized in the middle piece of sperm that may inhibit or interfere with mitochondria and ultimately affect the motility of sperm. Exposure of adult rats to 2 mg/kg Cd for 24 hr. induced the ROS and catalase activity and also inhibit the TGF- β3 response and p38 MAPK phosphorylation [123, 124]. Role of tyrosine-phosphorylated dihydrolipoamide dehydrogenase (DLD) was reported in capacitation, hyperactivation and acrosome reaction in hamster [37, 125] after Cd exposure of 1.2 mg/kg BW that induce tyrosine phosphorylation of DLD leads to lower the dehydrogenase activity, and thus affect the mitochondria and sperm motility. Only few studies are reported the effect of Cd during sperm capacitation. As capacitation process involve the influx of Ca2+ ions, thereby in presence of Cd which is also having similar charge as Ca, may mimic or replace the Ca entry by competitive binding and, thus affecting the capacitation process. More research is warranted to find out the molecular mechanism of Cd toxicity on capacitation in different species with different doses.
