Infertility and other untoward reproductive and developmental outcomes, such as spontaneous abortion, fetal and neonatal death, birth defects, and genetic susceptibilities to cancer and other diseases, are associated with genetic damage occurring in mammalian germ cells. This Project employs molecular biomarkers in the identification and characterization of chemicals in our environment that are responsible for such germ cell damage. Specifically, fluorescence in situ hybridization (FISH) with chromosome specific DNA markers are used to detect structural and numerical chromosome damage in sperm and early embryonic cells of rodents. These rodent sperm-FISH assays, which provide parallel models of similar sperm-FISH assays in humans, are being used for evaluating the aneugenic and clastogenic potential of environmental chemicals tested in NTP bioassays, as well as for addressing questions about dose response, differential stage sensitivity, the relationship of defects seen in sperm to those transmitted to the early embryo, and other important issues related to health-risks which cannot be addressed in human studies. During this past year, frozen samples of mouse sperm were obtained from RACB studies of Di- and Tri-bromonitromethane and from numerous 90-day Toxicity Studies of NTP compounds. SBIR projects developing automated methods for scoring these sperm samples are near successful completion.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Intramural Research (Z01)
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U.S. National Inst of Environ Hlth Scis
United States
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Marchetti, Francesco; Bishop, Jack B; Cosentino, Lidia et al. (2004) Paternally transmitted chromosomal aberrations in mouse zygotes determine their embryonic fate. Biol Reprod 70:616-24
Frias, Sara; Van Hummelen, Paul; Meistrich, Marvin L et al. (2003) NOVP chemotherapy for Hodgkin's disease transiently induces sperm aneuploidies associated with the major clinical aneuploidy syndromes involving chromosomes X, Y, 18, and 21. Cancer Res 63:44-51
Marchetti, F; Bishop, J B; Lowe, X et al. (2001) Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse. Proc Natl Acad Sci U S A 98:3952-7
Schmid, T E; Lowe, X; Marchetti, F et al. (2001) Evaluation of inter-scorer and inter-laboratory reliability of the mouse epididymal sperm aneuploidy (m-ESA) assay. Mutagenesis 16:189-95
Marchetti, F; Lowe, X; Bishop, J et al. (1999) Absence of selection against aneuploid mouse sperm at fertilization. Biol Reprod 61:948-54