Assessing the health care needs of the aged.
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Biomedical subjects
Publications and source records attributed to R L Berg.
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Previously, we reported that in vitro exposure of murine embryos to 0.1 microg/ml o,p'-DDT (an estrogenic pesticide) significantly reduced development to blastocyst and mean cell number per embryo, and increased percent cell death by 96 h of culture. The objective of the present study was to determine if developmental injury induced by o,p'-DDT resulted from estrogenic, antiestrogenic, or unrelated adverse biologic mechanisms. Toward this objective, pronuclear embryos from CD-1 mice were cultured 96 h in medium supplemented with 0.1% ethanol (control) or 0.1 microg/ml o,p'-DDT, 17beta-estradiol, or ICI 182,780 dissolved in ethanol as single agents or as paired mixtures. As single agents, development to blastocyst and mean cell numbers were significantly reduced and percent apoptosis was significantly increased for embryos cultured in the presence of o,p'-DDT or ICI 182,780. Development to blastocyst was significantly reduced for embryos cultured in the presence of 17beta-estradiol. Beneficial interaction occurred when the receptor antagonist ICI 182,780 was combined with either receptor agonist (o,p'-DDT or 17beta-estradiol). In contrast, interaction was not significant when the two agonists were combined. The results indicate that developmental injury due to the estrogenic pesticide o,p'-DDT was abolished by the addition of the receptor antagonist ICI 182,780 and not by the receptor agonist 17beta-estradiol. The findings underscore the utility of the model for uncovering mechanisms of developmental injury.
Culturing pronuclear embryos from CD-1 mice with o,p'-DDT and p,p'-DDT was examined as a means for directly evaluating toxicant risk and for increasing the speed of screening developmental toxicants. Pronuclear (2PN) embryos from CD-1 mice were cultured 96 h in modified Earle's balanced salt solution containing 0.1% (v/v) ethanol (control) or 10-fold dilutions of 17/beta-estradiol, o,p'-DDT, or p,p'-DDT. Compared to control treatment, 96 h incubation of 2PN embryos with 0.1 gg/mL o,p'-DDT significantly reduced embryo development to blastocyst and mean cell number, and increased the percentage of cells undergoing apoptosis. The effects of o,p'-DDT on developmental parameters were dose-responsive. Embryo sexing by multiplex polymerase chain reaction indicated that both sexes were susceptible to toxicant injury with comparable reduction in development to blastocyst (27% and 24%, respectively) in the presence of o,p'-DDT. Results of this study suggest that in vitro exposure of preimplantation embryos to xenobiotics may provide a useful tool for rapidly screening developmental toxicants.
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