Estradiol-chlordecone (Kepone) interactions: Additive effect of combinations for uterotropic and embryo implantation functions

Chlordecone (Kepone) is a polychlorinated hydrocarbon that has a low affinity for the estrogen receptor. Although the compound has been shown to be an estrogen antagonist for some responses within the central nervous system, and in hypophyseal gonadotrophic cells, such an action for other responses has not been reported. In the present study ovariectomized immature rats were used to determine the uterotropic effects of chlordecone in the presence or absence of estradiol. Administration of 30 mg/kg chlordecone per day for 3 days increased the response to 0.01, 0.1 and 1 μg/kg per day of estradiol benzoate (EB). No additive or inhibitory effect was found with chlordecone plus 10 μg/kg EB. Likewise, the uterine response to 15 or 30, but not 45, mg/kg chlordecone was enhanced by the co-administration of 0.1 μg/kg EB. A second response, initiation of embryo implantation in hypophysectomized, progesterone-primed, delayed implanting pregnant rats was tested. Subliminal doses of estradiol or chlordecone were additive for initiating normal implantation in more than 80% of the animals. The results indicate that chlordecone is not an estrogen antagonist for functions that require the action of the estrogen receptor in the uterus. The mechanism(s) involved in the additive action have not been determined but emphasize the need to consider xenoestrogen-natural estrogen interactions when assessing risks for reproductive toxi.