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GENE ARRAYS FOR ELUCIDATING MECHANISTIC DATA FROM MODELS OF MALE INFERTILITY AND CHEMICAL EXPOSURE IN MICE, RATS AND HUMANS
Citation:
Rockett, J C. AND D J. Dix. GENE ARRAYS FOR ELUCIDATING MECHANISTIC DATA FROM MODELS OF MALE INFERTILITY AND CHEMICAL EXPOSURE IN MICE, RATS AND HUMANS. Presented at Society of Toxicology, Nashville, TN, March 17 - 21, 2002.
Description:
Gene arrays for elucidating mechanistic data from models of male infertility and chemical exposure in mice, rats and humans
John C. Rockett and David J. Dix
Gamete and Early Embryo Biology Branch, Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Abstract
By comparing gene expression profiles from the testes or sperm of fertile and infertile humans with those from corresponding mouse models, it may be possible to identify genes or gene networks that are similarly altered in both species. This approach could be useful in understanding both congenital infertility and that derived from environmental toxicants. To this end, commercially available membrane arrays were used to compare human testicular RNA from infertile patients with different stages of spermatogenic arrest, with mouse testicular RNA from strains with equivalent pathologies. Although the data obtained from this approach provided some insight into the status of gene expression in adult testes, the percentage of informative genes was relatively low. This is because off-the-shelf arrays are generally of utilitarian design, and often cannot accommodate the requirements of focused research, such as targeting gene expression in a specific tissue. Consequently, we also developed a custom mouse testis expression cDNA array containing 950 genes, and used it to examine the molecular mechanisms of male infertility in a number of different model systems. Despite the success of this custom testis array, rapid progress in gene identification and annotation and the development of other array formats means that the future of such tissue-specific cDNA arrays is uncertain. Instead, there is increasing interest in utilizing large sets of DNA oligonucleotide probes. Relatively large sets of oligonucleotide probes from named genes are already available for mouse, rat and human, and it is likely that more genes and species will become available as existing and new genome sequencing projects are completed and begun. (This is an abstract of a proposed presentation and does not necessarily reflect EPA policy).