Abstract

BackgroundFor over sixty years, it has been known that mammalian spermatozoa immediately after ejaculation are virtually infertile. They became able to fertilize only after they reside for long time (hours to days) within female genital tract where they complete their functional maturation, the capacitation. This process is finely regulated by the interaction with the female environment and involves, in spermatozoa, a myriad of molecules as messengers and target of signals. Since, to date, a model able to represent the molecular interaction that characterize sperm physiology does not exist, we realized the Human Sperm Interactme Network3.0 (HSIN3.0) and its main component (HSNI3.0_MC), starting from the pathway active in male germ cells.ResultsHSIN3.0 and HSIN3.0_MC are scale free networks, adherent to the Barabasi-Albert model, and are characterised by an ultra-small world topology. We found that they are resistant to random attacks and that are designed to respond quickly and specifically to external inputs. In addition, it has been possible to identify the most connected nodes (the hubs) and the bottlenecks nodes. This result allowed us to explore the control mechanisms active in driving sperm biochemical machinery and to verify the different levels of controls: party vs. date hubs and hubs vs. bottlenecks, thanks the availability of data from KO mice. Finally, we found that several key nodes represent molecules specifically involved in function that are thought to be not present or not active in sperm cells, such as control of cell cycle, proteins synthesis, nuclear trafficking, and immune response, thus potentially open new perspectives on the study of sperm biology.ConclusionsFor the first time we present a network representing putative human sperm interactome. This result gives very intriguing biological information and could contribute to the knowledge of spermatozoa, either in physiological or pathological conditions.

Highlights

  • For over sixty years, it has been known that mammalian spermatozoa immediately after ejaculation are virtually infertile

  • Mammalian spermatozoa are known to acquire their fertilizing ability only after a long and complex series of biochemical modification that recognises different steps. It starts within the testis, with spermatogenesis, and continues in epididymis, where spermatozoa undergo a series of important chemical modifications, and it culminates with a process, called capacitation, that occurs within the female genital tract

  • The final step of our work was the realization of HSIN3.0, composed by 25 connected components, 7891 nodes and 14,712 links, which represent the most complete evolution of Human spermatozoa Interactiome network (HSIN)

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Summary

Introduction

It has been known that mammalian spermatozoa immediately after ejaculation are virtually infertile They became able to fertilize only after they reside for long time (hours to days) within female genital tract where they complete their functional maturation, the capacitation. Mammalian spermatozoa are known to acquire their fertilizing ability only after a long and complex series of biochemical modification that recognises different steps It starts within the testis, with spermatogenesis, and continues in epididymis, where spermatozoa undergo a series of important chemical modifications, and it culminates with a process, called capacitation, that occurs within the female genital tract. It is clear that peculiar biological features characterize male gametes: virtually they are transcriptionally silent, their cytosol is absent, and they are the only cellular typology that exert its function in an organism other than that produced them They adapted their biochemical machinery to these conditions and evolved a complex control strategy. They are able to physiologically responding to physical and chemical

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