Animal models of prenatal exposure to diethylstilboestrol

Animals of several species exposed perinatally to diethylstilboestrol (DES) have been evaluated for anomalies and tumours. In male offspring, anomalies of the testis and epididymis have been reported, but evidence for tumours has been very limited. Many anomalies and tumours have been recorded in female offspring, and some of these duplicate the anomalies and tumours reported in DES-exposed women, whereas others either have not yet been discovered or else do not occur in the human species. A variety of abnormal physiological responses has been identified in animals exposed perinatally to DES. There were altered levels of hormones and receptors; responses to postnatal injection of hormones were often modified; and an increased susceptibility to other carcinogens has been established. Several mechanisms have been postulated to explain tumour production later in life after perinatal exposure to DES. Deficiencies in immune function indicate a mechanism of impaired immune surveillance. The presence of DES and its metabolites in the fetus and neonate raise the issue of somatic mutation. Evidence for sister chromatid exchange, cell transformation in tissue culture and other toxic effects on chromosomes support the somatic mutation hypothesis. A third hypothesis is involvement of abnormal differentiation of the hypothalamus. Structural, hormonal and behavioural changes support this idea. Possible additional problems in humans after exposure to DES, on the basis of animal model studies, are increased tumour frequency with ageing and transmission of cancer risk to the third generation. The multigeneration effect of DES provides a model to test the mechanism of transmission of cancer risk from one generation to the next. The outcome of such experiments could have considerable impact on the understanding of the association between DES and cancer specifically and transplacental cancer generally.