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Are zona pellucida genes involved in recurrent oocyte lysis observed during in vitro fertilization?

  • Gamete Biology
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Complete oocyte lysis in in vitro fertilization (IVF) is a rare event, but one against which we remain helpless. The recurrence of this phenomenon in some women in each of their IVF attempts, regardless of treatment, together with the results of animal experiments led us to investigate the possible involvement of the genes encoding for the glycoproteins constituting the zona pellucida (ZP).

Patients & methods

Over the last ten years, during which we treated over 500 women each year, three women suffered recurrent oocyte lysis during their IVF attempts in our Centre for Reproductive Biology. For each of these three cases, we sequenced the four genes and promoter sequences encoding the glycoproteins of the ZP. The sequence variations likely to cause a change in protein expression or structure, were investigated in a control group of 35 women who underwent IVF without oocyte lysis and with normal rates of fertilization.

Results & conclusion

We found no mutations in the ZP genes sequenced. Only some polymorphisms present in the control group and in the general population were detected, excluding their specific involvement in the phenotype observed. Thus, although we suspected that complete oocyte lysis was due to a genetic cause, it did not seem possible to directly incriminate the genes encoding the proteins of the ZP in the observed phenotype. Further study of the genes involved in the processing and organization of ZP glycoproteins may allow elucidation of the mechanism underlying recurrent oocyte lysis during in vitro fertilization.

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References

  1. Hoodbhoy T, Joshi S, Boja ES, Williams SA, Stanley P, Dean J. Human sperm do not bind to rat zonae pellucidae despite the presence of four homologous glycoproteins. J Biol Chem. 2005;280:12721–31.

    Article  CAS  PubMed  Google Scholar 

  2. Wassarman P, Chen J, Cohen N, Litscher E, Liu C, Qi H, et al. Structure and function of the mammalian egg zona pellucida. J Exp Zool. 1999;285:251–8.

    Article  CAS  PubMed  Google Scholar 

  3. Neganova IE, Sekirina GG, Eichenlaub-Ritter U. Surface-expressed E-cadherin, and mitochondrial and microtubule distribution in rescue of mouse embryos from 2-cell block by aggregation. Mol Hum Reprod. 2000;6:454–64.

    Article  CAS  PubMed  Google Scholar 

  4. Kurotaki Y, Hatta K, Nakao K, Nabeshima Y, Fujimori T. Blastocyst axis is specified independently of early cell lineage but aligns with the ZP shape. Science. 2007;316:719–23.

    Article  CAS  PubMed  Google Scholar 

  5. Wassarman PM, Mortillo S. Structure of the mouse egg extracellular coat, the zona pellucida. Int Rev Cytol. 1991;130:85–110.

    Article  CAS  PubMed  Google Scholar 

  6. Gilchrist RB, Lane M, Thompson JG. Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update. 2008;14:159–77.

    Article  CAS  PubMed  Google Scholar 

  7. Rankin TL, O’Brien M, Lee E, Wigglesworth K, Eppig J, Dean J. Defective zonae pellucidae in Zp2-null mice disrupt folliculogenesis, fertility and development. Development. 2001;128:1119–26.

    CAS  PubMed  Google Scholar 

  8. Lefievre L, Conner SJ, Salpekar A, Olufowobi O, Ashton P, Pavlovic B, et al. Four zona pellucida glycoproteins are expressed in the human. Hum Reprod. 2004;19:1580–6.

    Article  CAS  PubMed  Google Scholar 

  9. Jimenez-Movilla M, Dean J. ZP2 and ZP3 cytoplasmic tails prevent premature interactions and ensure incorporation into the zona pellucida. J Cell Sci. 2011;124:940–50.

    Article  CAS  PubMed  Google Scholar 

  10. Wassarman PM. Zona pellucida glycoproteins. Annu Rev Biochem. 1988;57:415–42.

    Article  CAS  PubMed  Google Scholar 

  11. Bleil JD, Wassarman PM. Structure and function of the zona pellucida: identification and characterization of the proteins of the mouse oocyte’s zona pellucida. Dev Biol. 1980;76:185–202.

    Article  CAS  PubMed  Google Scholar 

  12. Greve JM, Wassarman PM. Mouse egg extracellular coat is a matrix of interconnected filaments possessing a structural repeat. J Mol Biol. 1985;181:253–64.

    Article  CAS  PubMed  Google Scholar 

  13. Goudet G, Mugnier S, Callebaut I, Monget P. Phylogenetic analysis and identification of pseudogenes reveal a progressive loss of zona pellucida genes during evolution of vertebrates. Biol Reprod. 2008;78:796–806.

    Article  CAS  PubMed  Google Scholar 

  14. Wassarman PM. Zona pellucida glycoproteins. J Biol Chem. 2008;283:24285–9.

    Article  CAS  PubMed  Google Scholar 

  15. Conner SJ, Lefievre L, Hughes DC, Barratt CL. Cracking the egg: increased complexity in the zona pellucida. Hum Reprod. 2005;20:1148–52.

    Article  CAS  PubMed  Google Scholar 

  16. Liu C, Litscher ES, Mortillo S, Sakai Y, Kinloch RA, Stewart CL, et al. Targeted disruption of the mZP3 gene results in production of eggs lacking a zona pellucida and infertility in female mice. Proc Natl Acad Sci U S A. 1996;93:5431–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Rankin T, Talbot P, Lee E, Dean J. Abnormal zonae pellucidae in mice lacking ZP1 result in early embryonic loss. Development. 1999;126:3847–55.

    CAS  PubMed  Google Scholar 

  18. Epifano O, Liang LF, Dean J. Mouse Zp1 encodes a zona pellucida protein homologous to egg envelope proteins in mammals and fish. J Biol Chem. 1995;270:27254–8.

    Article  CAS  PubMed  Google Scholar 

  19. Liang LF, Dean J. Conservation of mammalian secondary sperm receptor genes enables the promoter of the human gene to function in mouse oocytes. Dev Biol. 1993;156:399–408.

    Article  CAS  PubMed  Google Scholar 

  20. Hughes DC, Barratt CL. Identification of the true human orthologue of the mouse Zp1 gene: evidence for greater complexity in the mammalian zona pellucida? Biochim Biophys Acta. 1999;1447:303–6.

    Article  CAS  PubMed  Google Scholar 

  21. Pokkyla RM, Lakkakorpi JT, Nuojua-Huttunen SH, Tapanainen JS. Sequence variations in human ZP genes as potential modifiers of zona pellucida architecture. Fertil Steril. 2011;95:2669–72.

    Article  PubMed  Google Scholar 

  22. Cordeiro I, Calhaz-Jorge C, Leal F, Barata M, Coelho AP. Fractured zona oocytes in in-vitro fertilization cycles stimulated with gonadotrophin-releasing hormone analogue and human menopausal gonadotrophin. Hum Reprod. 1993;8:609–11.

    CAS  PubMed  Google Scholar 

  23. Paz G, Amit A, Yavetz H. Case report: pregnancy outcome following ICSI of oocytes with abnormal cytoplasm and zona pellucida. Hum Reprod. 2004;19:586–9.

    Article  PubMed  Google Scholar 

  24. Kipersztok S, Osawa GA, Liang LF, Modi WS, Dean J. POM-ZP3, a bipartite transcript derived from human ZP3 and a POM121 homologue. Genomics. 1995;25:354–9.

    Article  CAS  PubMed  Google Scholar 

  25. Margalit M, Paz G, Yavetz H, Yogev L, Amit A, Hevlin-Schwartz T, et al. Genetic and physiological study of morphologically abnormal human zona pellucida. Eur J Obstet Gynecol Reprod Biol. 2012;165:70–6.

    Article  CAS  PubMed  Google Scholar 

  26. Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2001;29:308–11.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491:56–65.

    Article  PubMed  Google Scholar 

  28. Shen Y, Stalf T, Mehnert C, Eichenlaub-Ritter U, Tinneberg HR. High magnitude of light retardation by the zona pellucida is associated with conception cycles. Hum Reprod. 2005;20:1596–606.

    Article  CAS  PubMed  Google Scholar 

  29. Bertrand E, Van den Bergh M, Englert Y. Does zona pellucida thickness influence the fertilization rate? Hum Reprod. 1995;10:1189–93.

    CAS  PubMed  Google Scholar 

  30. Gabrielsen A, Lindenberg S, Petersen K. The impact of the zona pellucida thickness variation of human embryos on pregnancy outcome in relation to suboptimal embryo development. A prospective randomized controlled study. Hum Reprod. 2001;16:2166–70.

    Article  CAS  PubMed  Google Scholar 

  31. Ebner T, Balaban B, Moser M, Shebl O, Urman B, Ata B, et al. Automatic user-independent zona pellucida imaging at the oocyte stage allows for the prediction of preimplantation development. Fertil Steril. 2009;94:913–20.

    Article  PubMed  Google Scholar 

  32. Madaschi C, Aoki T, de Almeida Ferreira Braga DP, de Cassia Savio Figueira R, Semiao Francisco L, Iaconelli Jr A, et al. Zona pellucida birefringence score and meiotic spindle visualization in relation to embryo development and ICSI outcomes. Reprod Biomed Online. 2009;18:681–6.

    Article  PubMed  Google Scholar 

  33. Cinar O, Demir B, Dilbaz S, Saltek S, Aydin S, Goktolga U. Does empty zona pellucida indicate poor ovarian response on intra cytoplasmic sperm injection cycles? Gynecol Endocrinol. 2012;28:341–4.

    Article  CAS  PubMed  Google Scholar 

  34. Stanger JD, Stevenson K, Lakmaker A, Woolcott R. Pregnancy following fertilization of zona-free, coronal cell intact human ova: case report. Hum Reprod. 2001;16:164–7.

    Article  CAS  PubMed  Google Scholar 

  35. Rankin T, Familari M, Lee E, Ginsberg A, Dwyer N, Blanchette-Mackie J, et al. Mice homozygous for an insertional mutation in the Zp3 gene lack a zona pellucida and are infertile. Development. 1996;122:2903–10.

    CAS  PubMed  Google Scholar 

  36. Wassarman PM, Qi H, Litscher ES. Mutant female mice carrying a single mZP3 allele produce eggs with a thin zona pellucida, but reproduce normally. Proc Biol Sci. 1997;264:323–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Bertrand E, Van den Bergh M, Englert Y. Clinical parameters influencing human zona pellucida thickness. Fertil Steril. 1996;66:408–11.

    CAS  PubMed  Google Scholar 

  38. Millar SE, Lader E, Liang LF, Dean J. Oocyte-specific factors bind a conserved upstream sequence required for mouse zona pellucida promoter activity. Mol Cell Biol. 1991;11:6197–204.

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Wassarman PM, Litscher ES. Biogenesis of the mouse egg’s extracellular coat, the zona pellucida. Curr Top Dev Biol. 2013;102:243–66.

    Article  CAS  PubMed  Google Scholar 

  40. Soyal SM, Amleh A, Dean J. FIGalpha, a germ cell-specific transcription factor required for ovarian follicle formation. Development. 2000;127:4645–54.

    CAS  PubMed  Google Scholar 

  41. Liang L, Soyal SM, Dean J. FIGalpha, a germ cell specific transcription factor involved in the coordinate expression of the zona pellucida genes. Development. 1997;124:4939–47.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to Kanaya Malkani for his critical reading and comments on the manuscript.

We thank Philippe Bonneau and Sandrine Lehais, technicians at the University Hospital of Angers, for their participation in gene sequencing.

Author information

Authors and Affiliations

  1. CNRS 6214/INSERM 1083, Université d’Angers, Angers cedex 9, France

    Marc Ferré, Patrizia Amati-Bonneau, Vincent Procaccio, Pascal Reynier & Pascale May-Panloup

  2. Laboratoire de Biochimie et Biologie Moléculaire, Centre Hospitalier Universitaire d’Angers, 49933, Angers cedex 9, France

    Marc Ferré, Patrizia Amati-Bonneau, Vincent Procaccio & Pascal Reynier

  3. Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire d’Angers, 49933, Angers cedex 9, France

    Catherine Morinière, Sophie Lemerle & Philippe Descamps

  4. Laboratoire de Biologie de la Reproduction, Centre Hospitalier Universitaire d’Angers, 49933, Angers cedex 9, France

    Véronique Ferré-L’Hôtellier & Pascale May-Panloup

  5. Centre PMA La Rochelle, 17000, La Rochelle, France

    Daniel Przyrowski

Authors
  1. Marc Ferré
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  2. Patrizia Amati-Bonneau
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  10. Pascale May-Panloup
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Corresponding author

Correspondence to Pascale May-Panloup.

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Contribution for each author

PMP, the principal investigator, takes primary responsibility for the paper. PMP, MF and PAB contributed to the conception, design and coordination of the research. CM and SL recruited the patients. PMP and MF contributed to the collection and analysis of data. PMP and MF contributed to writing the manuscript. PMP, MF, PAB, CM, VFL, SL, VP, PD and PR contributed to drafting the article and revising it, approving of the final version.

Capsule Recurrent oocyte lysis during in vitro fertilization does not seem to be due to any abnormality of zona pellucida genes

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Ferré, M., Amati-Bonneau, P., Morinière, C. et al. Are zona pellucida genes involved in recurrent oocyte lysis observed during in vitro fertilization?. J Assist Reprod Genet 31, 221–227 (2014). https://doi.org/10.1007/s10815-013-0141-8

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  • DOI: https://doi.org/10.1007/s10815-013-0141-8

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