The spermatozoa caught in the net: the biological networks to study the male gametes post-ejaculatory life

BACKGROUND: Mammalian spermatozoa, immediately after the ejaculation are unable to fertilize the oocyte. To reach their fertilizing ability the male gametes must complete a process of functional maturation, the capacitation, within the female genital tract. Only once the capacitation is completed the spermatozoa can respond to the oocyte interaction with the exocytosis of acrosome content, acrosome reaction (AR). These post-ejaculatory events are under the attention of Researchers from more than fifty years but their basic knowledge is still unsatisfactory. This failure could be due not to the insufficiency of available data, but to the inability to manage them in a descriptive model. Thus, to overlap this problem, the capacitation and the AR were represented using the biological networks formalism. In addition the effect of elimination from both the networks of the most linked (the hubs) or of random selected nodes was verified and the network representing the common element of capacitation and AR (C∩A) was realized. RESULTS: The statistical analysis of resulting graphs showed that capacitation, AR and C∩A networks follow the scale free topology and are characterized by low clustering. In all cases it was possible to identify the key molecules (Ca(2+), ATP, P-Tyr, PKA, PLD1 in capacitation, Ca(2+), ATP in AR and C∩A) and to describe their role in signalling transduction. The effect of hubs elimination caused the collapse of networks structure, while the elimination of random selected nodes did not affected it. CONCLUSIONS: It was demonstrated that the post-ejaculatory life of male gametes is a series of events characterised by a high signalling efficiency and robustness against random failure. This strengthens the evidence that the adoption of biological networks modellization of capacitation and AR could increase the understanding of spermatozoa physiology, potentially opening new perspective in drug discovery, diagnosis and therapy of male infertility.