Capacitation-Related Lipid Remodeling of Mammalian Spermatozoa Membrane Determines the Final Fate of Male Gametes: A Computational Biology Study

Abstract

To become fully fertile, mammalian spermatozoa must undergo a complex process of biochemical maturation within the female genital tract, which determines a marked lipid remodeling (LR) of membranes. Here, we represent this process as a biological network, which is a graph constituted by nodes (the molecules involved in LR) and by edges (their interactions). As a result, we found that LR network has a scale-free and small world topology. This implies that it is robust against random damage and that it allows a fast and specific transmission of information. In addition, the hubs in the network allow identification of the control mechanisms involved in membrane-related signaling, which could concur in determining the fate of ejaculated spermatozoa. Interestingly, different pathways involved in LR (maintenance of functional incompetence, reaching of fertilizing ability, apoptosis) are overlapped and some molecules take part in different signalling cascades; thus their role in sperm biology needs to be interpreted in a more large context. In addition, it was possible to differentiate, either based on their topological and biological characteristics, the molecules acting as global or local controller in LR. These findings may contribute to the understanding of capacitation-related signaling and of sperm physiopathology.