Tumor volumes were measured, analyzed and represented graphically

It would be interesting to further explore 1472969 how G5555 cost spermatozoa fix the membranous breakage 12826236 when CDs are shed. The fact that CDs are present exclusively on epididymal spermatozoa suggests that CDs may have a role unique to epididymal sperm maturation. Earlier studies identified activities of several classes of enzymes, including lysosomal hydrolases and intermediate metabolic enzymes in CDs of rat, rabbit, ram and bovine spermatozoa. Most of those enzymes are confirmed in our proteomic analyses, thus supporting the earlier hypothesis that CDs may have a role in energy metabolism during epididymal sperm maturation. The CD purification procedure provided us with an opportunity to evaluate differences between CD-bearing and CD-free epididymal spermatozoa. The notion that CDs are required for ATP production is consistent with and supported by our findings that CDs are enriched with various metabolic enzymes involved in ATP production. The dynamic changes of pyruvate levels in CD-bearing spermatozoa further support that CDs may represent an organelle with active energy metabolism, which can be largely abolished when CDs are absent or removed. Taken together, CDs appear to serve as an energy source, which provides energy required for the ongoing maturation of epididymal spermatozoa. Numerous molecular and cellular events occur during epididymal sperm maturation, including exposure of surface lipids and proteins followed by modifications, changes in the acrosome membrane, modification of the nucleus, incorporation of glycolytic enzymes into the flagellum, etc.. Typical protein modifications during epididymal sperm maturation include tyrosine phosphorylation and serine/ threonine phosphorylation. Interestingly, many phosphatase are also enriched in CDs, such as PPP1CC, PRSS21 and PRSS52, which are all involved in protein serine/ threonine phosphorylation, and SORD, a protease associated with protein tyrosine phosphorylation, was also highly enriched in CDs. Thus, CDs also appear to provide modifying enzymes for sperm protein modifications. The finding that CDs are required for the “fueling” process through which materials required for energy metabolic pathways are integrated into and stored in various sub- compartments of the flagellum is consistent with the fact that both glycolytic inhibitors and genetic inactivation of key glycolytic enzymes can abolish sperm competence for developing progressive motility. It has been suggested that sperm mitochondria remain largely inactive during epididymal sperm maturation because minimal membrane potential can be detected, and our data confirmed this phenomenon. Interestingly, mitochondria become gradually activated during epididymal sperm maturation, and by the time spermatozoa reach the cauda epididymis, the mitochondrial membrane potential reaches to levels comparable to that of HTF-activated spermatozoa. Physiologically, this may suggest that mitochondria undergo a “priming” process, through which inactive mitochondria become activated and thus competent for producing energy through the oxidative phosphorylation system in conjunction with active glycolysis within the flagellum. This is also supported by a previous report showing that the knockout male mice lacking transaldolase, one of many enzymes enriched in CDs, displayed abnormal mitochondria with no detectable membrane potential, and consequently immotile spermatozoa and male infertility. Given that mitochondria of epididymal spermatozoa are mostly