Acrosome reaction: relevance of zona pellucida glycoproteins

Abstract

During mammalian fertilisation, the zona pellucida (ZP) matrix surrounding the oocyte is responsible for the binding of the spermatozoa to the oocyte and induction of the acrosome reaction (AR) in the ZP-bound spermatozoon. The AR is crucial for the penetration of the ZP matrix by spermatozoa. The ZP matrix in mice is composed of three glycoproteins designated ZP1, ZP2 and ZP3, whereas in humans, it is composed of four (ZP1, ZP2, ZP3 and ZP4). ZP3 acts as the putative primary sperm receptor and is responsible for AR induction in mice, whereas in humans (in addition to ZP3), ZP1 and ZP4 also induce the AR. The ability of ZP3 to induce the AR resides in its C-terminal fragment. O-linked glycans are critical for the murine ZP3-mediated AR. However, N-linked glycans of human ZP1, ZP3 and ZP4 have important roles in the induction of the AR. Studies with pharmacological inhibitors showed that the ZP3-induced AR involves the activation of the G i -coupled receptor pathway, whereas ZP1-and ZP4-mediated ARs are independent of this pathway. The ZP3-induced AR involves the activation of T-type voltage-operated calcium channels (VOCCs), whereas ZP1-and ZP4-induced ARs involve both T-and L-type VOCCs. To conclude, in mice, ZP3 is primarily responsible for the binding of capacitated spermatozoa to the ZP matrix and induction of the AR, whereas in humans (in addition to ZP3), ZP1 and ZP4 also participate in these stages of fertilisation. Keywords: acrosome reaction; fertilisation; oocyte; signalling pathways; spermatozoa; zona pellucida glycoproteins INTRODUCTION Mammalian fertilisation is a highly synchronized process that involves a complex series of interactions between the spermatozoon and the egg, culminating in their unison. The initial steps in fertilisation involves the binding of the spermatozoon to the zona pellucida (ZP) matrix surrounding the egg, followed by induction of the acrosome reaction (AR) in the zona-bound spermatozoon, a pre-requisite for penetration of the ZP matrix by the spermatozoon. The spermatozoon acrosome is a Golgi-derived organelle that forms a cap over the anterior two-thirds of its nucleus. The AR involves the fusion of the sperm membrane with the outer acrosomal membrane, resulting in release of the acrosomal contents and exposure of the inner acrosomal membrane on the anterior head of the spermatozoon. Various physiological agents, such as progesterone, serum albumin, follicular fluid, hormones (including biogenic amines), hydrolytic enzymes (particularly proteases), hyaluronic acid and ZP glycoproteins, have been implicated in the induction of the AR. [1][2][3] In the present paper, we review the role of the ZP matrix and its constituents in AR induction. Various downstream signalling pathways involved in the ZP glycoprotein-induced AR will also be discussed. On the basis of the current literature and studies from our group, the salient differences in the ZP glycoprotein-mediated induction of the AR in mouse versus human will be highlighted.

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

“…This role of ZP3 is confirmed by the experimental evidence that its removal causes the loss of function of SERB in mouse model: the ZP3 -/-mice are infertile. ZP2, in mice, are unable to interfere with sperm-egg binding or with induction of the AR, and monoclonal and polyclonal antibodies anti-ZP2 do not affect the initial binding of the sperm to the oocyte, whereas they are significantly able to inhibit the binding of acrosome-reacted sperm to the ZP (Gupta and Bhandari, 2011). This suggests that ZP2 could act as a secondary receptor for sperm during fertilization (Bleil et al, 1988).…”

“…In humans, ZP1 has a 638-aa polypeptide backbone; ZP2 has 745 aa; ZP3 has 424 aa, and ZP4 has 540 aa. In all cases, the ZP proteins are heavily glycosylated, having N-and O-linked glycans (Gupta and Bhandari, 2011). ZP3, in the mouse model, represents the higher affinity ligand for spermatozoa, and it is the primary site for the two gametes interaction.…”

Fucose, Mannose, and β-N-Acetylglucosamine Glycopolymers Initiate the Mouse Sperm Acrosome Reaction through Convergent Signaling Pathways

“…26,38,39 In these mechanisms, ZP is thought to bind to at least two receptors on the sperm membrane. One is a G-protein coupled receptor, which is reported to regulate adenylyl cyclase and activate PKA, phospholipase C (PLC) β1, and H + efflux.…”

Fertility control to mitigate human–wildlife conflicts: a review

“…There are four major ZP glycoproteins, named ZP1, ZP2, ZP3 and ZP4, each with different functions in the oocyte-sperm binding process and with varying degrees of homology among mammalian species (e.g. Kitchener et al 2009;Gupta and Bhandari 2011). These differences are partly responsible for the variable results obtained when using a particular ZP vaccine on different species and have been exploited to make ZP-based vaccines more specific (Kitchener et al 2009;Levy 2011).…”