Mechanisms of Reproductive Tract Toxicity

Many studies have demonstrated that perinatal exposure to DES interferes with the normal differentiation of both female and male reproductive tract. Although the mechanisms are not completely understood, epigenetic and/or genetic components may be involved. Recent studies [36, 37] have suggested a molecular mechanism responsible for the structural alterations observed in oviduct, uterus, cervix, and vagina. Cellular changes may also be closely linked to these structural alterations. Furthermore, we have described permanent abnormal gene imprinting in which neonatal exposure to DES causes demethyla-tion of an estrogen-responsive gene in the mouse uterus [38]. We are currently investigating the relationship of this finding to tumor induction.

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