Three-dimensional structure of the zona pellucida

The zona pellucida is the extracellular coat that surrounds the mammalian oocyte. It forms a spherical shell of remarkably uniform thickness (5-10 microns in eutherian mammals). The mouse is currently the largest source of data on the zona pellucida and this review is built largely on these data. The zona pellucida is composed of three proteins in both mice and humans: ZP1, ZP2 and ZP3. These proteins are glycosylated and, in mice, have mature relative molecular masses of 200,000, 120,000 and 83,000, respectively. ZP1 is a dimer of two apparently identical subunits. All three mouse proteins have been sequenced and possess transmembrane domains at their C-terminal ends coupled with furin cleavage sites immediately upstream. Sequence data have been used to provide an accurate assessment of the mole ratios of the three proteins. The ratio of ZP2:ZP3 is close to 1:1, whereas ZP1 is approximately 9% of the combined mole amounts of ZP2 and ZP3. Ultrastructural evidence suggests that the mouse zona pellucida is composed of filaments constructed by head-to-tail association of globular proteins. The coordinate synthesis of the three zona pellucida proteins coupled with the near 1:1 stoichiometry of ZP2 and ZP3 is consistent with a model in which ZP2-ZP3 heterodimers are the basic repeating units of the filament, with cross-linking of filaments by dimeric ZP1. This model is also consistent with data from ZP2 and ZP3 gene knockout and antisense experiments. However, the structure remains unproven. The small amount of ZP1 relative to ZP2 and ZP3 may have important implications for the distribution of ZP1 cross-links, since the number of cross-linking sites potentially exceeds the number of ZP1 dimer molecules by a considerable margin. The evidence that ZP1, ZP2 and ZP3 are all synthesized via a membrane-bound step is discussed and two models are proposed for the assembly of the zona pellucida. The cortical reaction and its effect on the zona pellucida are examined in detail. It is shown that the amount of material released by cortical granules could be of the order of 30% by mass of ZP1, and that if this material was distributed predominantly on the inner face of the zona pellucida, its local concentration could approach that of ZP1. A model in which the zona block to polyspermy is caused by direct titration of zona pellucida binding sites is suggested as an alternative to the explanation that relies on enzyme cleavage of ZP2 to ZP2f. Finally, some of the major experimental and structural issues that remain to be addressed are identified.

This article has been cited by other articles:

				G.V. Sireesha, R.W. Mason, M. Hassanein, S. Tonack, A. Navarrete Santos, B. Fischer, and P.B. Seshagiri Role of cathepsins in blastocyst hatching in the golden hamster Mol. Hum. Reprod., June 1, 2008; 14(6): 337 - 346. [Abstract] [Full Text] [PDF]

				D. A. Gook, D.H. Edgar, J. Borg, and M. Martic Detection of zona pellucida proteins during human folliculogenesis Hum. Reprod., February 1, 2008; 23(2): 394 - 402. [Abstract] [Full Text] [PDF]

				P. Coy, L. Grullon, S. Canovas, R. Romar, C. Matas, and M. Aviles Hardening of the zona pellucida of unfertilized eggs can reduce polyspermic fertilization in the pig and cow Reproduction, January 1, 2008; 135(1): 19 - 27. [Abstract] [Full Text] [PDF]

				S. A. Williams, L. Xia, R. D. Cummings, R. P. McEver, and P. Stanley Fertilization in mouse does not require terminal galactose or N-acetylglucosamine on the zona pellucida glycans J. Cell Sci., April 15, 2007; 120(8): 1341 - 1349. [Abstract] [Full Text] [PDF]

				C. A Swann, S. J B Cooper, and W. G Breed Molecular evolution of the carboxy terminal region of the zona pellucida 3 glycoprotein in murine rodents Reproduction, April 1, 2007; 133(4): 697 - 708. [Abstract] [Full Text] [PDF]

				Y. Shen, T. Stalf, C. Mehnert, U. Eichenlaub-Ritter, and H.-R. Tinneberg High magnitude of light retardation by the zona pellucida is associated with conception cycles Hum. Reprod., June 1, 2005; 20(6): 1596 - 1606. [Abstract] [Full Text] [PDF]

				M. Mannikko, R.-M. Tormala, T. Tuuri, A. Haltia, H. Martikainen, L. Ala-Kokko, J.S. Tapanainen, and J.T. Lakkakorpi Association between sequence variations in genes encoding human zona pellucida glycoproteins and fertilization failure in IVF Hum. Reprod., June 1, 2005; 20(6): 1578 - 1585. [Abstract] [Full Text] [PDF]

				M. Jimenez-Movilla, M. Aviles, M. J. Gomez-Torres, P. J. Fernandez-Colom, M. T. Castells, J. de Juan, A. Romeu, and J. Ballesta Carbohydrate analysis of the zona pellucida and cortical granules of human oocytes by means of ultrastructural cytochemistry Hum. Reprod., August 1, 2004; 19(8): 1842 - 1855. [Abstract] [Full Text] [PDF]

				N. Bausek, H. H. Ruckenbauer, S. Pfeifer, W. J. Schneider, and F. Wohlrab Interaction of Sperm with Purified Native Chicken ZP1 and ZPC Proteins Biol Reprod, August 1, 2004; 71(2): 684 - 690. [Abstract] [Full Text] [PDF]

				K. Bogner, K.-D. Hinsch, P. Nayudu, L. Konrad, C. Cassara, and E. Hinsch Localization and synthesis of zona pellucida proteins in the marmoset monkey (Callithrix jacchus) ovary Mol. Hum. Reprod., July 1, 2004; 10(7): 481 - 488. [Abstract] [Full Text] [PDF]

				L. Lefievre, S.J. Conner, A. Salpekar, O. Olufowobi, P. Ashton, B. Pavlovic, W. Lenton, M. Afnan, I.A. Brewis, M. Monk, et al. Four zona pellucida glycoproteins are expressed in the human Hum. Reprod., July 1, 2004; 19(7): 1580 - 1586. [Abstract] [Full Text] [PDF]

				T. Hoodbhoy and J. Dean Insights into the molecular basis of sperm-egg recognition in mammals Reproduction, April 1, 2004; 127(4): 417 - 422. [Abstract] [Full Text] [PDF]

				Y. Yang, A. Balla, N. Danilovich, and M. R. Sairam Developmental and Molecular Aberrations Associated with Deterioration of Oogenesis During Complete or Partial Follicle-Stimulating Hormone Receptor Deficiency in Mice Biol Reprod, October 1, 2003; 69(4): 1294 - 1302. [Abstract] [Full Text] [PDF]

				C. L. Kerr, W. F. Hanna, J. H. Shaper, and W. W. Wright Characterization of Zona Pellucida Glycoprotein 3 (ZP3) and ZP2 Binding Sites on Acrosome-Intact Mouse Sperm Biol Reprod, June 1, 2002; 66(6): 1585 - 1595. [Abstract] [Full Text] [PDF]

				T. Ebner, M. Moser, C. Yaman, M. Sommergruber, J. Hartl, K. Jesacher, and G. Tews Prospective hatching of embryos developed from oocytes exhibiting difficult oolemma penetration during ICSI Hum. Reprod., May 1, 2002; 17(5): 1317 - 1320. [Abstract] [Full Text] [PDF]

				M. El-Mestrah, P. E. Castle, G. Borossa, and F. W.K. Kan Subcellular Distribution of ZP1, ZP2, and ZP3 Glycoproteins During Folliculogenesis and Demonstration of Their Topographical Disposition Within the Zona Matrix of Mouse Ovarian Oocytes Biol Reprod, April 1, 2002; 66(4): 866 - 876. [Abstract] [Full Text] [PDF]

				S. M. Kiefer and P. Saling Proteolytic Processing of Human Zona Pellucida Proteins Biol Reprod, February 1, 2002; 66(2): 407 - 414. [Abstract] [Full Text] [PDF]

				C. D. Thaler and R. A. Cardullo Distinct Membrane Fractions from Mouse Sperm Bind Different Zona Pellucida Glycoproteins Biol Reprod, January 1, 2002; 66(1): 65 - 69. [Abstract] [Full Text]

				A. Mishra and P.B. Seshagiri Evidence for the involvement of a species-specific embryonic protease in zona escape of hamster blastocysts Mol. Hum. Reprod., November 1, 2000; 6(11): 1005 - 1012. [Abstract] [Full Text] [PDF]

				K. A. Eidne, C. C. Henery, and R. J. Aitken Selection of Peptides Targeting the Human Sperm Surface Using Random Peptide Phage Display Identify Ligands Homologous to ZP3 Biol Reprod, November 1, 2000; 63(5): 1396 - 1402. [Abstract] [Full Text]

				G. Vanroose, H. Nauwynck, A. V. Soom, M.-T. Ysebaert, G. Charlier, P. V. Oostveldt, and A. de Kruif Structural Aspects of the Zona Pellucida of In Vitro-Produced Bovine Embryos: A Scanning Electron and Confocal Laser Scanning Microscopic Study Biol Reprod, February 1, 2000; 62(2): 463 - 469. [Abstract] [Full Text]

				S. Greenhouse, P. E. Castle, and J. Dean Antibodies to human ZP3 induce reversible contraception in transgenic mice with `humanized' zonae pellucidae Hum. Reprod., March 1, 1999; 14(3): 593 - 600. [Abstract] [Full Text] [PDF]

				J.M. Bedford Mammalian Fertilization Misread? Sperm Penetration of the Eutherian Zona Pellucida Is Unlikely to be a Lytic Event Biol Reprod, December 1, 1998; 59(6): 1275 - 1287. [Full Text]

				H. Qi, Z. Williams, and P. M. Wassarman Secretion and Assembly of Zona Pellucida Glycoproteins by Growing Mouse Oocytes Microinjected with Epitope-tagged cDNAs for mZP2 and mZP3 Mol. Biol. Cell, February 1, 2002; 13(2): 530 - 541. [Abstract] [Full Text] [PDF]