Zona Pellucida Glycoproteins

Abstract

All mammalian eggs are surrounded by a relatively thick extracellular coat, the zona pellucida, that plays vital roles during oogenesis, fertilization, and preimplantation development. The mouse zona pellucida consists of three glycoproteins that are synthesized solely by growing oocytes and assemble into long fibrils that constitute a matrix. Zona pellucida glycoproteins are responsible for species-restricted binding of sperm to unfertilized eggs, inducing sperm to undergo acrosomal exocytosis, and preventing sperm from binding to fertilized eggs. Many features of mammalian and non-mammalian egg coat polypeptides have been conserved during several hundred million years of evolution.The plasma membrane of mammalian and non-mammalian eggs is surrounded by at least one extracellular coat. A zona pellucida (ZP) 2 surrounds mammalian oocytes, ovulated eggs, and embryos up to the early blastocyst stage of development. The ZP appears during oocyte growth, and blastocyst stage embryos hatch from the ZP prior to implanting in the uterus.Important roles have been ascribed to the ZP during oogenesis, fertilization, and preimplantation development (1, 2). For example, during fertilization, the ZP regulates binding of sperm to ovulated eggs and induces bound sperm to undergo cellular exocytosis, the acrosome reaction. The ZP also prevents binding of sperm to fertilized eggs. Removal of the ZP results in direct exposure of the egg plasma membrane to sperm and allows sperm from heterologous species to fuse with eggs. During preimplantation development, the ZP influences alignment of the embryonic-abembryonic axis and first cleavage plane (3). The ZP also ensures the integrity of preimplantation embryos as they traverse the female reproductive tract. Characteristics of the ZPAll mammalian eggs possess a ZP, although its thickness (ϳ1-25 m) and protein content (ϳ1-30 ng) vary considerably for eggs from different species (4). The mouse egg ZP is ϳ6.2 m thick and contains ϳ3.5 ng of protein (Fig. 1). The ZP is an elastic porous coat penetrable by antibodies, enzymes, and small viruses. All ZPs are composed of long interconnected fibrils that can be solubilized by mild acid or base, heat, or reducing agents. ZP glycoproteins (ZPGs) are held together in fibrils by noncovalent interactions. Characteristics of ZPGsThree glycoproteins, mZP1 (ϳ200 kDa), mZP2 (ϳ120 kDa), and mZP3 (ϳ83 kDa), compose the mouse egg ZP (4). The human egg ZP consists of four glycoproteins, hZP1 (ϳ100 kDa), hZP2 (ϳ75 kDa), hZP3 (ϳ55 kDa), and hZP4 (ϳ65 kDa) (5, 6). Three or more glycoproteins related to mZP1-3 are found in the ZP of eggs from a wide variety of mammalian species. In mice, mZP2 and mZP3 account for Ͼ80% of the mass of the ZP. ZPGs are heterogeneously glycosylated with asparagine-linked (N-) and serine/threonine-linked (O-) oligosaccharides. These cause ZPGs to migrate as broad bands on SDS-PAGE, and because the oligosaccharides are sialylated and sulfated, ZPGs have low isoelectric points. mZP1-3 possess four, six, and five N-linked oligosaccha...

Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy

“…Zinc-mediated crosslinks could also have roles later in preimplantation embryo development as the embryo travels along the oviduct, enters the mitotic phase, and prepares for implantation. 1, 9, 78, 79 Coordinate covalent bonds formed between zinc and these side chains constitute strong yet labile bonds that can break and reform depending on the stresses placed upon them, giving a dynamic structure that may be necessary for it to adapt to the dividing embryo. Although there is no structural data for ZP1 a structure of the ZP2 ZP-C domain is available.…”

“…10, 11 The ZP provides a rigid and defined volume for the dividing zygote as it proceeds through numerous cell divisions during pre-implantation embryo development. 9, 10 …”

Mutant ZP1 in Familial Infertility

“…In mouse models, oocytes have been shown to secrete only three zona pellucida proteins (ZP1, ZP2, and ZP3), 1 and it has been proposed that the zonae pellucidae of mice and humans are similar in structure. 13 In mice, long filaments of repeating ZP2–ZP3 units are cross-linked by ZP1 (which has 70% homology with human ZP1) to form a meshlike matrix.…”

“…1A). 1 It is vital for the production of oocytes in early development, 2 for fertilization 3 (e.g., in gamete recognition at the zona pellucida 4 and in the prevention of polyspermia), and for the protection of early embryos before implantation. 5 In mice, the targeted knockout of either the gene encoding ZP2 or the gene encoding ZP3 precludes the development of a zona pellucida, leading to sterility.…”

Can mammalian mothers influence the sex of their offspring peri-conceptually?

“…Although the functions of the ZP may include responsibility for species specificity and facilitation of the acrosome reaction, Wassarman (2008) wrote 'many important issues related to the participation of the ZP glycoproteins in the fertilisation process remain unresolved or controversial'. At the same time, he noted that such processes are likely to be highly conserved 'during several hundred million years of evolution'.…”