Differential effects of dichlorodiphenyltrichloroethane analogs, chlordecone, and 2,3,7,8-tetrachlorodibenzo-p-dioxin on establishment of pregnancy in the hypophysectomized rat.
Many of the organochlorine pesticides have been shown to elicit estrogenic responses in laboratory animals. Two estrogenic actions, initiation of implantation and maintenance of pregnancy, were examined in progesterone-primed, delayed-implanting, hypophysectomized rats exposed to several polychlorinated hydrocarbons. The insecticide P,P'-dichlorodiphenyltrichloroethane (DDT) was nearly devoid of estrogenic activity for initiating implantation, as was a dichloro analog, 1,1-dichloro-2-[p-chlorophenyl],2-[o-chlorophenyl]ethane (O,P'-DDD), but another such analog, 1,1-dichloro-2-(p-chlorophenyl),2-(o-chlorophenyl)ethylene (O,P'-DDE), was nearly as estrogenic as the O,P'-DDT isomer of DDT and the methoxylated analog methoxychlor. The latter three compounds not only initiated implantation, but maintained pregnancy when given in large (200 mg/kg) and repeated doses. Another insecticide, chlordecone (Kepone) was more estrogenic than any of the DDT analogs and maintained pregnancy with a single dose of 50 mg/kg. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a toxic contaminant of herbicide production, did not induce implantation at a dose of 125 micrograms/kg, but inhibited the implantation initiated by estrone in 35% of the animals. The mechanism of this antiestrogenicity is unknown but most probably does not involve direct action via the classical estrogen receptor. The possible interference with the normal blastocyst-uterine interactions of these polychlorinated xenobiotics may be an important factor in their being considered reproductive toxins.
Johnson
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Department of Gynecology and Obstetrics, University of Kansas Medical Center, Ralph L. Smith Research Center, Kansas City 66103.
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Dey
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D000818:Animals; D001755:Blastocyst / Q000187:drug effects; D007631:Chlordecone / Q000494:pharmacology*; D003634:DDT / Q000494:pharmacology*; D003633:Dichlorodiphenyl Dichloroethylene / Q000494:pharmacology*; D010064:Embryo Implantation / Q000187:drug effects*; D004970:Estrone / Q000494:pharmacology; D005260:Female; D007016:Hypophysectomy; D008731:Methoxychlor / Q000494:pharmacology*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects / Q000502:physiology*; D051381:Rats
D000072317:Polychlorinated Dibenzodioxins; D004970:Estrone; D003633:Dichlorodiphenyl Dichloroethylene; D003634:DDT; D007631:Chlordecone; D008731:Methoxychlor