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Profiling the placenta
Gene expression in mouse embryonic and placental tissues
Edward R. Winstead

In May, researchers at the US National Institute of Aging completed construction of a DNA library comprising some 15,000 mouse genes, many of which play a role in early development. Bits of DNA from the library were arrayed on slides, or microarrays, that are used to measure the activity of these genes in mouse tissue. This week, the Institute reports the results of its first experimental use of the microarrays: an attempt to characterize gene activity in the earliest stages of mammalian life.

Detail from microarray. Gene expression levels in the placenta are red and those in the embryo are green.

The study compared the activity of the 15,000 genes in mouse placental and embryonic tissues halfway through gestation. An analysis showed that 720 genes displayed statistically significant differences in expression between the embryo and the placenta. From this group of genes, the researchers identified nearly 300 that are "more highly expressed" in the placenta—roughly five times the number of genes previously reported to be active in the placenta.

"The 15,000-gene mouse microarray is a unique resource," says Minoru S.H. Ko, who runs the Institute's Developmental Genomics and Aging Section. "Our group has been trying to assemble this library of genes for nearly ten years." Similar efforts, he notes, have not focused on genes involved in early development. Upon completion of the library, the researchers calculated that roughly 80 percent of the genes were previously unidentified and therefore not represented in available libraries.

Creating the library involves collecting genetic material from expressed genes. "It's relatively easy to obtain this material during adult stages of development," says Ko. "But generating sufficient material from genes that are uniquely expressed during the embryonic stage is more difficult." The tiny size of mice embryos made the work all the harder.

Recent studies have linked placental defects to failed pregnancies

Although collecting genetic material in mice embryos is a challenge, doing so in humans is impossible at present. Even if laws that prohibit some researchers from working on human embryonic tissue are revoked, the technical challenges will remain. For example, researchers have no way to study in humans the earliest stages of cell differentiation after egg fertilization. The results of this study appear in the current issue of Proceedings of the National Academy of Sciences.

Ko's decision to profile the placenta was influenced by recent research on the organ. Defects in the placenta, through which nutrients and oxygen reach the embryo, have been linked to failed pregnancies. Another reason for the profile was simply to gain information: the mechanisms of placental development and the number of genes that are placenta-specific are unknown.

Interest in microarray technology has increased greatly in the last year. Cancer researchers, for example, are using microarrays to develop gene expression profiles for different kinds of tumor cells and as possible diagnostic tools. Ko's team is working on the next generation mouse microarray for profiling early development, which may contain 30,000 genes.

As soon as the library was completed in May, the Institute of Aging sent the gene set to ten research centers worldwide. The plan is to develop a database of information on gene expression and early development.

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Tanaka, T.S. et al. Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray. Proc Natl Acad Sci USA 97, 9127-9132 (August 1, 2000).

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