Functional features and protein network of human sperm-egg interaction

Abstract

Elucidation of the sperm-egg interaction at the molecular level is one of the unresolved problems in sexual reproduction, and understanding the molecular mechanism is crucial in solving problems in infertility and failed in vitro fertilization (IVF). Many molecular interactions in the form of protein-protein interactions (PPIs) mediate the sperm-egg membrane interaction. Due to the complexity of the problem such as difficulties in analyzing in vivo membrane PPIs, many efforts have failed to comprehensively elucidate the fusion mechanism and the molecular interactions that mediate sperm-egg membrane fusion. The main purpose of this study was to reveal possible protein interactions and associated molecular function during sperm-egg interaction using a protein interaction network approach. Different databases have been used to construct the human sperm-egg interaction network. The constructed network revealed new interactions. These included CD151 and CD9 in human oocyte that interact with CD49 in sperm, and CD49 and ITGA4 in sperm that interact with CD63 and CD81, respectively, in the oocyte. These results showed that the different integrins in sperm may be involved in human spermegg interaction. It was also suggested that sperm ADAM2 plays a role as a protein candidate involved in sperm-egg membrane interaction by interacting with CD9 in the oocyte. Interleukin-4 receptor activity, receptor signaling protein tyrosine kinase activity, and manganese ion transmembrane transport activity are the major molecular functions in sperm-egg interaction protein network. The disease association analysis indicated that spermegg interaction defects are also reflected in other disease networks such as cardiovascular, hematological, and breast cancer diseases. By analyzing the network, we identified the major molecular functions and disease association genes in sperm-egg interaction protein. Further experimental studies will be required to confirm the significance of these new computationally resolved interactions and the genetic links between sperm-egg interaction abnormalities and the associated disease.

Expression and distribution of CD151 as a partner of alpha6 integrin in male germ cells

“…The existence of the CD151 tetraspanin network in the equatorial segment of sperm and their interaction with the α6 subunit of presented α6β4/β1 integrin suggest a possibility of trans-interaction of both sperm and egg protein networks during sperm-egg membrane fusion. This is emphasized by the previously reported interaction between CD151 and CD9 tetraspanins in human oocyte with α3 integrin (CD49C) in spermatozoa 50 . Because the CD151 is most probably localized in the membrane environment, offering only the relatively small extracellular part to an interaction, the predicted N-terminal integrin domain contacts would correspond to an integrin interaction in its closed, www.nature.com/scientificreports www.nature.com/scientificreports/ folded state.…”

Identification of putative drug targets for human sperm-egg interaction defect using protein network approach

“…Information found in PPIs databases supports the construction of interaction networks. All retrieved data from the various data sources (refer to [ 4 , 5 ]) were combined and loaded into Cytoscape 2.8 [ 13 ] to construct the protein interaction network (PIN). Two PINs for sperm proteins and oocyte proteins have been created, and then intersection (overlapping) network has been constructed using a network modification plugin (compare two networks) in Cytoscape.…”

“…Two PINs for sperm proteins and oocyte proteins have been created, and then intersection (overlapping) network has been constructed using a network modification plugin (compare two networks) in Cytoscape. Because our primary aim was to identify protein candidates involved in sperm-egg interactions, we extracted only the proteins that contain a signal sequence and/or transmembrane domain [ 14 ] by selecting signal peptide and transmembrane features from sequence annotation (features) in an extensively curated UniProt database ( www.uniprot.org ) (for more details refer to [ 4 , 5 ]).…”

“…Due to detection of the molecules that immediate human membrane sperm-oocyte interaction, different experimental methods have been carried out [ 3 ]. In our previous research (refer to [ 4 , 5 ]), we have represented that in addition to experimental techniques, computational methods, protein interaction network approach, can address protein-protein interactions between human sperm and egg; we have shown the links between the sperm and egg proteins in the form of a protein interaction network. Several research questions associated with the function of single or groups of interacting proteins can be answered with the help of protein-protein interaction (PPI) networks [ 6 ].…”

Role of Tetraspanin CD9 Molecule in Fertilization of Mammals

“…Rubinstein et al (1996) found out that CD9 as well as CD63, CD81 and CD82 organize a complex with other associated molecules as the VLA integrins and HLA-DR antigens. Recently, interactions between CD9 and CD49B, CD63 and IZUMO1 during human fertilization were predicted using several computational approaches (Sabetian et al 2014). Some authors (Ellerman et al 2003) concluded CD9 as a receptor for PSG17 (a member of pregnancy-specific glycoprotein family), which, similar to IZUMO, is a member of the immunoglobulin superfamily.…”