Chapter Ten - The Mouse Egg's Zona Pellucida
Section snippets
Introduction to the Zona Pellucida
Nearly all animal cells are surrounded by an acellular component called the extracellular matrix (ECM) that participates in a myriad of biological activities (Alberts et al., 2014). ECM affects gene expression, differentiation, morphogenesis, cellular adhesion, cellular migration, and intercellular communication. Integrins are transmembrane receptors that mediate interactions between ECM and intracellular actin cytoskeleton, permitting outside-in and inside-out signal transduction. Most cells
Oogenesis in Mice
The ZP is laid down during the process of oogenesis in females that results in production of unfertilized eggs (Gosden, 2013; Rodrigues, Limback, McGinnis, Plancha, & Albertini, 2008; Wassarman & Albertini, 1994; Zuccotti, Merico, Cecconi, Redi, & Garagna, 2011) (Fig. 1A). In mice oogenesis begins early in fetal development with appearance of 15–100 primordial germ cells (PGCs) in yolk sac endoderm and in the region of the allantois arising from the primitive streak. PGCs migrate into the
Zona Pellucida Proteins
The mouse egg's ZP is a gel-like structure that is composed of three proteins, called ZP1–3, that have apparent MWs of about 200, 120, and 83 kDa, respectively, and account for virtually all proteins (3.5 ng) in the ZP (Bleil & Wassarman, 1980a; Litscher & Wassarman, 2015; Wassarman, 1988a) (Fig. 3). ZP2 and ZP3 are present in roughly equimolar amounts in the ZP and are monomers, whereas ZP1 is the least abundant protein and is a dimer of identical polypeptide chains held together by
Zona Pellucida Domain Proteins
All three mouse ZP proteins possess a zona pellucida domain (ZPD)—ZP1, amino acids (aa) 271–540; ZP2, aa 364–628; and ZP3, aa 45–302. ZP1–3 are prototypical ZPD proteins (Bork & Sander, 1992) that are present in virtually all vertebrate egg ZP and VE, as well as in a wide variety of tissues and organs in both vertebrates and invertebrates (Jovine, Darie, Litscher, & Wassarman, 2005; Litscher & Wassarman, 2015; Plaza, Chanut-Delalande, Fernandes, Wassarman, & Payre, 2010). The ZPD arose more
Zona Pellucida Protein Synthesis
Are oocytes, follicle cells, or both the site of synthesis of mouse ZP proteins? This question was resolved in the early 1980s using growing oocytes, with or without surrounding follicle cells, cultured in vitro in the presence of radiolabeled aa or sugars. It was concluded that ZP proteins are synthesized only by growing mouse oocytes, not by follicle cells (Bleil & Wassarman, 1980b; Greve, Salzmann, Roller, & Wassarman, 1982; Salzmann, Greve, Roller, & Wassarman, 1983; Shimizu, Tsuji, & Dean,
Zona Pellucida-Knockout Mice
With the advent of gene targeting procedures mouse lines have been established in which ZP genes have been inactivated by homologous recombination and insertional mutagenesis. Homozygous null males are unaffected by the mutations. Oocytes and eggs from mutant females carrying a single ZP3 allele (heterozygous nulls; ZP3+/−) possess a ZP and the females reproduce normally (Table 1). However, the ZP is less than one-half the thickness (2.7 ± 1.2 μm) of wild-type ZP (6.2 ± 1.9 μm) and contains about
Zona Pellucida Protein Secretion and Assembly
Certain elements involved in secretion of ZP proteins by growing oocytes are located in the CTP. One of these elements is the CFCS that must be cleaved by a proprotein convertase for secretion of ZP proteins to take place (Litscher & Wassarman, 1999; Williams & Wassarman, 2001). When the CFCS is mutated, it abolishes cleavage and results in accumulation of unprocessed ZP proteins in the ER. Under these conditions, secretion of ZP proteins is reduced as much as 20-fold, but the low level of
Zona Pellucida and Fertilization
For sperm to fertilize ovulated eggs they must bind to and penetrate the ZP, reach the egg's plasma membrane, and fuse with it. To penetrate the ZP, acrosome-intact (AI) sperm must first bind to the ZP and undergo the acrosome reaction (ARx) (Buffone, Hirohashi, & Gerton, 2014), a process that involves multiple membrane fusions (Wassarman & Litscher, 2008). The ARx is a Ca2 +-dependent event that leads to signaling through sperm G proteins to produce intracellular ionic changes and second
Summary
(1) Mouse and all other mammalian eggs are surrounded by a relatively thick, gel-like ECM called the ZP. (2) The mouse egg's ZP is composed of three unique proteins, ZP1–3, encoded by single-copy genes on different chromosomes. (3) ZP genes are expressed solely by growing mouse oocytes and, therefore, only by female mice. (4) ZP1–3 are prototype ZPD proteins that are synthesized and processed only by growing oocytes and secreted for self-assembly into fibrils and matrix. (5) ZP2 and ZP3
Acknowledgments
Many thanks to the postdoctoral fellows, graduate students, and research assistants who contributed to our research on ZP proteins and mammalian fertilization at Harvard Medical School, Roche Institute of Molecular Biology, and Icahn School of Medicine at Mount Sinai. Our research was supported in part by the National Institutes of Health (NICHD) and by Hoffmann-La Roche Inc.
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2022, F and S ScienceCitation Excerpt :In the iGC-zona-intact oocyte aggregates, we did not observe overt mitochondria transport into the GV oocytes (Fig. 3B, C). Because the zona thickness of the growing oocytes may reach 6.2 μm (34), it was reasonable to speculate that the zona pellucida might obstruct organelle transport between iGCs and oocytes. To test this, we placed zona-free GV oocytes on iGCs in GDF9-containing media.