Diethylstilbestrol Metabolism by the Fetal Genital Tract

Abstract

Oxidative metabolism of diethylstilbestrol (DES) [associated with vaginal adenocarcinoma in women whose mothers received it during pregnancy] was measured in both the male and female genital tracts of the fetal mouse in organ culture. The major oxidative metabolite formed was Z,Z-dienestrol, whose formation appeared to be time dependnet in the isolated fetal genital tract of both sexes. This peroxidative metabolite, which was previously linked to bioactivation of DES in adult target tissues, was not detected in the fetal liver cultures. In addition, fetal genital tracts were capable of O-methylation of DES. In fact, a new metabolite, 4''-O-methyl-DES, was formed in fetal genital tissues but not in liver cultures. Conjugation of DES occurred extensively in the fetal liver and placenta but not in the fetal genital tissues; conjugated DES was found primarily in the media. The fetal genital tract, which is the primary target for the transplacental carcinogenicity of DES, has the capacity to metabolize this compound.