Molecular mechanism of irreversible changes in target organs induced by perinatal hormone exposure

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Perinatal exposure of estrogens to mice during a critical period induces irreversible changes in various reproductive organs. Estrogen receptor α (ERα) has been demonstrated to be essential in induction of persistent changes in the mouse vagina. Microarray analyses demonstrate various up-regulated genes in the vagina of mice exposed perinatally to estrogens. Methylation status of growth factor related genes is not altered, however, one gene which suppress function of ERα is methylated and showing low expression. Methylation of this gene results in its low expression, thus, ERα is free from suppression, which may result in persistent activation of ERα. The persistently activated ERα induces expression of growth factor related genes which stimulate persistent cell proliferation in the mouse vagina.