Heterotopic columnar epithelium and adenosis in the vagina of the mouse after neonatal treatment with clomiphene citrate.

Physiologically, the epithelium of the mouse vagina undergoes conversion during early postnatal life from columnar to stratified squamous. A similar process in the human occurs in the late first and early second trimesters of pregnancy. The mouse vagina has been identified as a good developmental model of the human. Previous work in the mouse has shown that this process is affected by neonatal administration of diethylstilbestrol. We have administered diethylstilbestrol and clomiphene citrate to parallel groups of BALB/c neonatal mice. They were followed up to 24 weeks. In both groups, persistent columnar or heterotopic columnar epithelium, not seen in the control mice, was identified and associated with adenosis. This effect of diethylstilbestrol and clomiphene citrate appears to be similar to the biologic response to transplacental diethylstilbestrol in the human. After transplacental diethylstilbestrol, malignant vaginal tumors rarely develop. If clomiphene citrate, given to the human prior to pregnancy to induce ovulation or by inadvertence during pregnancy, were to circulate into the critical time of vaginal differentiation, a similar biologic potential may exist. The first situation seems to be unlikely. The second is of more concern.