Possible involvement of CD81 in acrosome reaction of sperm in mice

Abstract

Tetraspanin CD81 is closely homologous in amino acid sequence with CD9. CD9 is well known to be involved in sperm-egg fusion, and CD81 has also been reported to be involved in membrane fusion events. However, the function of CD81 as well as that of CD9 in membrane fusion remains unclear. Here, we report that disruption of the mouse CD81 gene led to a reduction in the fecundity of female mice, and CD81-/- eggs had impaired ability to fuse with sperm. Furthermore, we demonstrated that when CD81-/- eggs were incubated with sperm, some of the sperm that penetrated into the perivitelline space of CD81-/- eggs had not yet undergone the acrosome reaction, indicating that the impaired fusibility of CD81-/- eggs may be in part caused by failure of the acrosome reaction of sperm. In addition, we showed that CD81 was highly expressed in granulosa cells, somatic cells that surround oocytes. Our observations suggest that there is an interaction between sperm and CD81 on somatic cells surrounding eggs before the direct interaction of sperm and eggs. Our results may provide new clues for clarifying the cellular mechanism of the acrosome reaction, which is required for sperm-egg fusion.

Extracellular vesicles and reproduction–promotion of successful pregnancy

“…The tetraspanin CD81 is expressed on the surface of the mouse oocyte 42 and surrounding somatic cells 43 and may also play a role in sperm-oocyte membrane fusion. 42,43,44 Subcellular expression of CD9 and CD81 in the mouse oocyte demonstrates that these are predominantly localized in the PVS and zona pellucida respectively.…”

“…42,43,44 Subcellular expression of CD9 and CD81 in the mouse oocyte demonstrates that these are predominantly localized in the PVS and zona pellucida respectively. It has been proposed that CD9 is primarily produced by the oocyte, whereas CD81 is primarily produced in the surrounding cumulus cells.…”

Genome-Wide Association Study Implicates Testis-Sperm Specific FKBP6 as a Susceptibility Locus for Impaired Acrosome Reaction in Stallions

“…Knockout and mutant rodent models have revealed 32 genotypes and 26 genes that are associated with impaired AR (IAR) phenotype (MGI: http://www.informatics.jax.org/). The AR involves genes for neurotransmitter receptors [11], [12], calcium channels [13], [14], [15], membrane fusions [16] and vesicle exocytosis [9], [17]. Mouse triple knockout models for five sperm motility and sperm-egg adhesion genes ( Tnp2 , H1.1 , H1t , Smcp ) suggest that AR might be the result of synergistic interaction of several genes [18].…”

Role of CD9 in Sperm–Egg Fusion and Virus-Induced Cell Fusion in Mammals

“…CD9 has cysteine-cysteine-glycine (CCG) residues (amino acids 152-154) as a tetraspanin-specifi c motif and two other cysteines within LEL Malaria sporozoites, a cell form that infects new hosts, are transmitted into the liver of the mammalian host through bites from infected mosquitoes, but the sporozoites fail to infect Cd81 −/− mouse hepatocytes, suggesting that CD81 is involved in sporozoite entry into hepatocytes as a host factor. Otherwise, Cd81 −/− female mice are subfertile, because Cd81 -defi cient eggs exhibit impaired sperm fusion ability (Rubinstein et al 2006 ;Tanigawa et al 2008 ). CD81 is expressed on Cd9 -defi cient eggs, and CD9 is also expressed on Cd81 -defi cient eggs at an expression rate comparable with that of wild-type eggs, indicating that CD9 and CD81 work independently in sperm-egg fusion (Ohnami et al 2012 ).…”