Fig. 6.1
Capacitation biological network. Actin polymerization (red node) interacts with (red arrows) all cellular compartments
6.4 Discussion
The biological results obtained in this study showed that sperm incubated with CD under capacitating conditions negatively affected the acquisition of fertilizing power. In fact, the coincubation of sperm with solubilized zonae pellucidae, physiological agonists of AR, was unable to promote exocytosis of acrosomal contents. However, the study of the main signal transduction pathways involved in this process showed that they were unaltered by the presence of CD but were efficient. The functional interpretation of these data can be inferred by analyzing the computational model, representing molecules involved in the postejaculatory maturation of the male gamete and their interactions and taking into account different intracellular locations. Through this innovative approach, it was possible to highlight how actin polymerization is the crucial node in the interconnection of various subcellular compartments. This event appears to be related to all metabolically active compartments in the sperm during capacitation (i.e., cytosol, membrane, cytoskeleton, mitochondria, and acrosome). It is also interesting to note that the only cellular compartment that has no relationship with actin polymerization is the nucleus, which, in sperm, remains silent until the moment of fertilization. Thus, it is clear that actin polymerization likely plays a role in the coordination between the various metabolic pathways, harmonizing their operation. In the case of inhibition of actin polymerization (in our work after treatment with CD), in fact, the individual signal transduction pathways are normally activated, but the acquisition of fertilizing power is compromised by their lack of coherence. The identification of the cytoskeleton as a factor involved in the inside-out signaling of sperm appears to be important. First, it is in line with recent observations made in other cellular models (Shafrir et al. 2000), ascribing to this structure a leading role in the evolution and implementation of cellular signaling, independent on its mechanical function. It could then reveal new analytical and descriptive approaches for the physiology of the male gamete. Finally, it could suggest new prognostic or therapeutic strategies in reproductive medicine.

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