Mammalian zona pellucida glycoproteins: structure and function during fertilization

Abstract

Zona pellucida (ZP) is a glycoproteinaceous translucent matrix that surrounds the mammalian oocyte and plays a critical role in the accomplishment of fertilization. In humans, it is composed of 4 glycoproteins designated as ZP1, ZP2, ZP3 and ZP4, whereas mouse ZP is composed of ZP1, ZP2 and ZP3 (Zp4 being a pseudogene). In addition to a variable sequence identity of a given zona protein among various species, human ZP1 and ZP4 are paralogs and mature polypeptide chains share an identity of 47%. Employing either affinity purified native or recombinant human zona proteins, it has been demonstrated that ZP1, ZP3 and ZP4 bind to the capacitated human spermatozoa and induce an acrosome reaction, whereas in mice, ZP3 acts as the putative primary sperm receptor. Human ZP2 only binds to acrosome-reacted spermatozoa and thus may be acting as a secondary sperm receptor. In contrast to O-linked glycans of ZP3 in mice, N-linked glycans of human ZP3 and ZP4 are more relevant for induction of the acrosome reaction. Recent studies suggest that Sialyl-Lewis(x) sequence present on both N- and O-glycans of human ZP play an important role in human sperm-egg binding. There are subtle differences in the downstream signaling events associated with ZP3 versus ZP1/ZP4-mediated induction of the acrosome reaction. For example, ZP3 but not ZP1/ZP4-mediated induction of the acrosome reaction is dependent on the activation of the Gi protein-coupled receptor. Thus, various studies suggest that, in contrast to mice, in humans more than one zona protein binds to spermatozoa and induces an acrosome reaction.

In vitro interaction of bovine herpesvirus 1 with uterine tube epithelial cells and oocytes

“…The ZP is comprised of three to five glycoproteins depending on the species. ZP proteins have been implicated in specific sperm binding of species, the prevention of polyspermy, and embryo protection between fertilization and implantation (Dunbar et al, 1991;Lasiene et al, 2009;Gupta et al, 2012;Yonezawa, 2014). However, there is a risk that virus particles could be trapped in the layers of the ZP (Vanroose et al, 2000;Van Soom et al, 2010).…”

Value Analysis of Sperm Spontaneous Acrosome Reaction in Male Fertility Evaluation

“…Recent studies of the acrosome reaction mainly concentrate on the acrosome reaction mechanism and molecular regulation mechanism [6][7][8][9], but there has been less research about the importance of the sperm spontaneous acrosome reaction and the relationship between the sperm spontaneous acrosome reaction and the sperm capability. In this paper, we will evaluate the significance of the sperm spontaneous acrosome reaction through analysis and study of SARR sperm and semen parameters.…”

Assisted Reproduction

“…31 In the human, capacitated sperm can be induced to undergo the acrosome reaction by ZP1, ZP2, and ZP4, although downstream signaling events may be different with ZP3 compared to ZP1 or ZP4. 32 In an early study, purified ZP3 blocked the ability of sperm to bind to the oocyte zona pellucida in a dose-dependent manner, implying that ZP3 is the zona pellucida sperm receptor, 33 and data from several other studies have implied that O-linked carbohydrate moieties underly the interaction of ZP3 and the sperm receptor. 34 Recently, the nature of this carbohydrate ligand has been further identified as the sialyl-Lewis sequence, a member of the selectin family.…”