Caspase and Capacitation

Capacitation is a prerequisite for sperm fertilization; it can be determined by hyper-activation and membrane changes. It has been demonstrated that capacitation reduced significantly the proportion of sperm with initiator caspase-9 and activator caspase-3. A significant negative correlation between capacitation and caspase-9 and -3 activation [29] has been also reported. It has been shown that spermatozoa with externalized phosphatidylserine have a significantly decreased potential to undergo capacitation and acrosome reaction [30] . There are two enzymes in primate sperm that are located between the sperm membrane and the acrosome; calpain and its natural inhibitor calpastatin [31]. Further studies showed that calpain activation is related to capacitation and the acrosome reaction [32] . Caspase-1 cleaves calpastatin and enhances the activity of calpains, which indicates a potential role for apoptosis signaling and caspase-1 in capacitation [33]. Prolactin has a prosurvival effect through its receptors in postacrosomal region, neck, mid piece, and principal piece of tail in sperm [34]. It has been demonstrated that a significant correlation exists between suppression of caspase activity and capacitation following use of prolactin.

12.2.4 Caspases and Male Infertility 12.2.4.1 Semen Parameters and Caspase

A significant association has been reported between caspase-3 activity and sperm morphology and motility [35]. It has been shown that nonapoptotic sperm that are negative for caspase-3 present with higher quality in terms of normal morphology [36]. Furthermore, spermatozoa of infertile patient have shown an increase in caspase activity [37]. Similarly, a significant negative correlation between sperm motility and viability and caspase-3 activation has been reported [38-43]. In a study that evaluates caspase enzymatic activity, semen fractions of infertile patients had higher caspase enzymatic activity compared to fractions in fertile controls [44] . Although there are significant correlation between caspase activation and the sperm quality regarding motility and vitality values, other contradictory results show no significant correlation between sperm morphology and caspase-3 activation [41].

12.2.4.2 DNA Fragmentation and Caspases

There are different mechanisms for sperm DNA fragmentation including damage by caspases. It appears that sometimes caspase activation is the main factor for DNA strand break during apoptosis in spermatogenesis [14, 45]. There are two forms of DNA strand breaks, single-strand DNA breaks that may be caused by oxygen radicals and could be repaired, and double-strand DNA break, which may be mediated by caspase and usually could not be repaired [46]. These findings highlight the possibility of an association between caspase activation and in vivo and in vitro male infertility. In support, it has been demonstrated that Caspase activity in epididymal and testis sperm has negatively correlated with ICSI outcome [45,47]. It has been proposed that selecting spermatozoa using specific preparation techniques could decrease the extent of sperm with DNA fragmentation and caspase expression [48].

12.2.4.3 Varicocele and Caspases

Apoptosis may play a role in the pathogenesis of infertility in men with varico-cele. Although comparison of apoptosis-related proteins between fertile and varicocele patients by immunoblotting did not show any difference for caspase-3 and Bcl2 expression, the amount of p53, PARP, and BAK expression in varicocele patient were significantly higher than fertile group [49]. It has been shown that hypoxia results in overexpression of Bcl2 and down-regulation of caspase-9 in internal spermatic vein of varicocele patients. Therefore, intrinsic pathway for apoptosis in varicocele patient could be hypothesized [50]. There was an increased expression of active caspase-3 in varicocele patients compared to fertile men. On the other hand, caspase-9 was detected in spermatogonia, spermato-cytes, and spermatids in varicocele patients, but not seen in these cells in the young fertile groups [51]. Indeed, both varicocele and aging are associated with high levels of ROS which cause DNA damage. PARP-1 is responsible for efficient repair of DNA and increased ROS can cause cessation of DNA repair and initiation of apoptosis [51].

12.2.4.4 Testicular Torsion and Caspases

Testicular torsion is a medical emergency that requires surgical intervention. Restoration of blood supply after torsion causes testicular ischemia-reperfusion injury which may lead to infertility [52]. It has been shown that testicular ischemia-reperfusion injury results in a marked increase in BAX, caspase-3, and caspase-9 following 24 h after reperfusion injury [53]. The organ damage also involves MAPK3/MAPK1 activation of the apoptotic machinery [53].

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100 Pregnancy Tips

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