The antiestrogen ICI 182,780 abolishes developmental injury for murine embryos exposed in vitro to o,p'-DDT(1)

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.