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Posted 02.23.06

MU Researchers Describe Protein's Role In Embryonic Development

COLUMBIA, Mo. -- A new discovery from University of Missouri-Columbia scientists about the formation of an embryo and a placenta before implantation could explain why cloning often fails in farm and laboratory animals. This could have large implications for in vitro fertilization techniques, which are widely used in human fertility procedures. The study was published in the Feb. 17 issue of Science

R. Michael Roberts, Mayandi Sivaguru, Kaushik Deb.R. Michael Roberts, Curators' Professor of Animal Sciences, and his team of researchers, found that when a mouse egg is fertilized and begins its cell division process, the first two cells are not created equal. One of the cells expresses a protein known as Cdx2. This cell will create others that form the placenta. The other cell, which does not express the protein, will form the fetus. The researchers predicted that any disruption of the Cdx2 expression may lead to an improperly formed placenta or a pregnancy failure. Disruption can occur when material is either injected or replaced in the cells, including during animal cloning techniques and in vitro fertilization procedures.

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"We have learned something fundamental about how embryos develop in mammals and how normal development might be accidentally impaired by cloning and in vitro fertilization techniques," Roberts said. "Some artificial reproduction technologies may be inherently damaging and convert a 'good' egg into a poor quality embryo. These findings and our future research may have considerable implications in how babies develop, whether they are mice or humans."

The research was performed in isolated mouse eggs and fertilized embryos by Kaushik Deb, a postdoctoral fellow under Roberts. Acquisitions of 2-D and 3-D images were done using advanced microscopes at the MU Molecular Cytology Core by Associate Director Mayandi Sivaguru. These findings also mark the first major results from a laser scanning microscope used in the Molecular Cytology Core, which is located in the Christopher S. Bond Life Sciences Center. Deb and Sivaguru said this discovery would not have been possible without the microscope. Around a dozen academic departments across the MU campus contributed to the purchase of the $650,000 system last year.

"These experiments require great skill in working with embryos that are only an eighth of a millimeter in diameter and much smaller than a pinhead," Roberts said. "The experience of recovering and growing the mice embryos, injecting them with chemicals that could knock down Cdx2 expression without killing the embryo, and using the confocal scanning microscope, were critical to the success of the experiments. Future research in the group will focus on defining other early markers of cell lineage specification and will include work on cow and pig as well as mouse embryos. The potential exists for improving pregnancy success after human IVF procedures." 

Funding for this research was provided by grants from the National Institutes of Health and the MU Food for the 21st Century Program.

Roberts holds a doctorate from Oxford University in England and joined MU in 1985. In 2005, Scientific American magazine named Roberts to its list of the top 50 research, business and policy leaders in the world for his work with human embryonic stem cells.



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