A model system to study the risk from chemical exposure to developing preimplantation embryos has been developed. Both short-term and long-term effects of such exposure can be studied. Traditionally, it was thought that exposure of pregnant females to toxic substances during the preimplantation period is without consequence either because the compound cannot reach the cleaving egg or because the embryo is killed by the exposure. We have looked at the effects of chemicals known to cause either birth defects or tumor formation. We have exposed preimplantation embryos (blastocysts) in vitro and have demonstrated a significant decrease in incorporation of radiolabeled precursors of RNA, DNA, and protein in viable, treated embryos. We know from specific labeling experiments that this compound is taken up by the mouse blastocyst. We hope soon to place exposed embryos in the uteri of pseudopregnant foster mothers. With such embryo transfer experiments, it will be possible to determine the effects of exposure to environmental carcinogens on implantation rate, birth rates and the relation of such exposure to birth defects. These techniques are easily applicable to other environmentally relevant compounds, in order to determine potential risk of exposure for the embryo in the early periods of development at a time when the pregnant mother is unaware of her pregnancy. The role of the endometrium in activating the carcinogens will be investigated utilizing endometrial cell-culture systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES003498-05
Application #
3250813
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1981-06-01
Project End
1987-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
School of Medicine & Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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Iannaccone, P M; Zhou, X; Khokha, M et al. (1992) Insertional mutation of a gene involved in growth regulation of the early mouse embryo. Dev Dyn 194:198-208
Ng, Y K; Iannaccone, P M (1992) Fractal geometry of mosaic pattern demonstrates liver regeneration is a self-similar process. Dev Biol 151:419-30
Ng, Y K; Iannaccone, P M (1992) Experimental chimeras: current concepts and controversies in normal development and pathogenesis. Curr Top Dev Biol 27:235-74
Iannaccone, P M; Van Gorder, M; Madsen, E L et al. (1991) The role of preimplantation sonographic exposure in postimplantation development and pregnancy outcome. J Ultrasound Med 10:659-64
Barch, D H; Jacoby, R F; Brasitus, T A et al. (1991) Incidence of Harvey ras oncogene point mutations and their expression in methylbenzylnitrosamine-induced esophageal tumorigenesis. Carcinogenesis 12:2373-7
Iannaccone, P M (1990) Fractal geometry in mosaic organs: a new interpretation of mosaic pattern. FASEB J 4:1508-12
Bossert, N L; Hitselberger, M H; Iannaccone, P M (1990) Protein alterations associated with N-methyl-N-nitrosourea exposure of preimplantation mouse embryos transferred to surrogate mothers. Teratology 42:147-56
Ng, Y K; Ohaki, Y; Deamant, F et al. (1990) Comparison of epidermal patch size in X-chromosome-linked mosaic and dizygotic chimeric mice. Cell Differ Dev 30:27-34

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