Izumo Protein Understanding the Molecular Term Paper

The failure of human hamster fusion in the presence of anti-human izumo antibody clearly showed that Human izumo protein is essential for fertilization.

This study however has raised some new questions. The difference in fertilization capacities between wild type and Izumo +/- type was not clearly discussed. Also, the fact that ICSI of izumo -/- produces twice as many litters as did the izumo +/- type implicates the possible role of other proteins, the expression of which is affected by the allele. That is to say that the mutant knockout sperm might have up-regulated or down regulated the expression of this unknown protein which may have aided the fertilization process as indicated by the statistics. [Katie Winter] contraceptive vaccine targeting the sperm is very much in prospect but much work is yet to be accomplished. A CD46 gene knockout as tried by the author in an earlier study did not result in defective sperm egg fusion. [Inoue et.al 2003] Similarly, ADAM1, ADAM2, ADAM3 gene knockout did not result in fusion defects but only exhibited problems in sperm zona binding. [Cho et, al 1998] a recent development of an immuno-contraceptive antigen for mice proved to be unsuccessful in spite of its success in vitro. [Wang et.al, 2008]

Conclusion

The process of fertilization is an intriguing one involving very many factors that leaves us awe in wonder at the complex molecular mechanisms involved in the formation of the embryo. Fertilization involves a variety of stages and every stage is important for the successful formation of the embryo. The discovery of the role of the izumo protein in the process of fertilization is therefore a remarkable breakthrough in our understanding of reproductive biology. This new discovery has opened new vistas for scientific research in the research on safe and cheaper contraceptives as well as providing a whole new dimension in our understanding of male infertility problems.Also, other results from the study such as the considerable variations in fertilization rates among izumo -/- and izumo +/- type sperms in the ICSI experiment shows the potential role of new proteins whose expression is influenced by the presence or absence of izumo protein. Thus, it is clear that we are still a long way from understanding the intricacies of fusion and post fusion events. It becomes vital to understand the other protein molecules that play a critical role in the fusion and fertilization process. However, there is no question of doubt that the discovery of the all-important role of the izumo protein in the egg-sperm fusion process has definitely furthered our knowledge and has taken us a step closer to fully understanding the biology of fertilization.

Bibliography

Wang, De Gang, Huang, Tian Hua, Xie, Quing Dong, an, Gang, (Mar 2008), 'Investigation of Recombinant mouse sperm protein Izumo as a potential immunocontraceptive agent', American Journal of Reproductive Immunology, Vol 59, No 3, pg. 225-234

Inoue N, Ikawa M, Nakanishi T, Matsumoto M, Nomura M, Seya T, Okabe M. (2003) Disruption of mouse CD46 causes an accelerated spontaneous acrosome reaction in sperm. Mol Cell Biol. 23: 2614 -2622

Cho C, Bunch DO, Faure JE, Goulding EH, Eddy EM, Primakoff P, Myles DG. (1998), 'Fertilization defects in sperm from mice lacking fertilin beta'. Science.281: 1857 -1859

Naz RK, Leslie MH, Zhu X. (2001) 'Inhibition of murine sperm-oolemma binding by antibodies to an oocyte membrane (OM) antigen: implication in contraceptive vaccine development'. Am J. Reprod Immunol. 45: 52 -61.

Katie Winter, 'Review Paper: The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs' retrieved 12th march 2008, at http://www.bio.davidson.edu/Courses/Molbio/MolStudents/spring2005/Winter/Review.htm

Naokazu Inoue, Masahito Ikawa, Ayako Isotani & Masaru

Okabe,(Mar 2005) 'The immunoglobulin superfamily protein

Izumo is required for sperm to fuse with eggs', Nature 434,….....