Biologic changes induced by unilateral intrauterine instillation of quinacrine in the rat and their reversal by either estradiol or progesterone.

In previous studies’ we have instilled cytotoxic agents and metabolic depressants into the endometrial cavity of rats, and have thereby induced changes in the endometrium which have resulted in reduced fertility. It was suggested that this reduction of fertility was due to an endometrial environment which was inadequate for implantation. Two different types of histologic changes have been observed. (1) Some chemical agents, such as cadmium and thio-TEPA (N, N’, N”-triethylene thiophosphoramide) have a marked capacity for inhibiting implantation, although they induce only slight morphologic alterations of the endometrium. Similar results were produced by physical noxia, such as freezing of the endometrium. 2 In the latter instance, depression of the capacity for implantation could be reversed by local application of histamine. 3 (2) Other cytotoxic substances such as monoiodacetate and ethanol produce intense morphologic changes which result in complete obliteration of the uterine lumen. The reduction of fertility in these animals was attributed primarily to mechanical obstruction. l The effects of cytotoxics as measured by implantation rates were reversible, except when extensive cicatricial lesions totally blocked the treated horn. Most of the drugs employed were inadequate for use in humans because of their potential toxicity.