Network Analyses of Sperm–Egg Recognition and Binding: Ready to Rethink Fertility Mechanisms?

Abstract

The rapid growth of published literature makes biomedical text mining increasingly invaluable for unpacking implicit knowledge hidden in unstructured text. We employed biomedical text mining and biological networks analyses to research the process of sperm egg recognition and binding (SERB). We selected from the literature the molecules expressed either on spermatozoa or on oocytes thought to be involved in SERB and, using an automated literature search software (Agilent Literature Search), we realized a network, SERBN, characterized by a hierarchical scale free and a small world topology. We used an integrated approach, either based on selection of hubs or by a cluster analysis, to discern the key molecules of SERB. We found that in most cases some of them are not directly situated on spermatozoa and oocyte, but are dispersed in oviductal fluid or embedded in exosomes present in the perivitelline space. To confirm and validate our results, we performed further analyses using STRING and Reactome FI software. Our findings underscore that the fertility is not a property of gametes in isolation, but rather depends on the functional integrity of the entire reproductive system. These observations collectively underscore the importance of integrative biology in exploring biological systems and in rethinking of fertility mechanisms in the light of this innovative approach.

Female-induced remote regulation of sperm physiology may provide opportunities for gamete-level mate choice

“…; Bernabò et al. ). In this way, females can remotely (and selectively) prepare sperm for fertilization before they reach the egg (Rosengrave et al.…”

“…Until now, sperm‐egg recognition and the acrosome reaction have traditionally been assumed to be mediated by the molecules expressed on the surfaces of eggs and sperm (Bernabò et al. ). However, recent studies have challenged this view by showing that many key fertilization molecules are not situated directly on gametes, but are dispersed through female (or egg)‐–derived fluids (Griffiths et al.…”

“…; Bernabò et al. ), thus encoding the molecular recognition between gametes. However, sperm glycan structures also moderate other processes that are critical for fertilization (Jiménez et al.…”

“…Despite increasing evidence for compatibility-based GMC, we lack an understanding of the mechanisms that underpin individual-specific interactions between eggs and sperm. While most attention has focused on gamete recognition systems that operate when sperm and eggs come into direct contact (Swanson and Vacquier 2002;Bernabò et al 2014), recent studies suggest that sperm selection can be influenced remotely prior to gamete contact by chemical signals released from eggs or (in internally fertilizing species) through sperm interactions with female reproductive tract fluids. For example, female reproductive secretions may mediate sperm selection to facilitate inbreeding avoidance in house mice (Firman and Simmons 2015) and internally fertilizing fish (Gasparini and Pilastro 2011), while egg-derived chemoattractants have been shown to differentially regulate sperm chemotaxis and sperm swimming behavior to favor sperm from genetically compatible males in externally fertilizing mussels Oliver and Evans 2014).…”

“…As with all cells, the sperm's glycan coat represents its outermost layer, and therefore any extracellular substances that come into contact with the sperm cell must first interact with this layer (Varki 2011;Lauc et al 2014). For example, during the fertilization process itself, sperm surface glycans (glycoproteins and other glycoconjugates) act as ligands for various egg surface molecules and egg-derived diffusible factors (Ohta et al 2000;Jiménez et al 2002;Hirohashi et al 2008;Bernabò et al 2014), thus encoding the molecular recognition between gametes. However, sperm glycan structures also moderate other processes that are critical for fertilization (Jiménez et al 2002;Hiyoshi et al 2007;Hirohashi et al 2008;Pang et al 2011;Hoshi et al 2012;Medina et al 2012;Bianchi et al 2014), including the regulation of sperm motility, sperm capacitation (functional activation of the spermatozoon) and in many species the acrosome reaction (i.e., prefertilization release of proteolytic enzymes from the sperm head) (Ohta et al 2000;Jiménez et al 2002;Diekman 2003;Liu et al 2012).…”