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

围产期雌激素暴露于小鼠的关键时期会导致各种生殖器官发生不可逆转的变化。雌激素受体α(ERα)在诱导小鼠阴道持续变化中起重要作用。基因芯片分析显示，在围产期暴露于雌激素的小鼠的阴道中，各种基因上调。生长因子相关基因的甲基化状态没有改变，但有一个抑制ERα功能的基因发生了甲基化，并表现出低表达。该基因的甲基化导致其低表达，因此ERα不受抑制，这可能导致ERα的持续激活。持续激活的ERα诱导生长因子相关基因的表达，从而刺激小鼠阴道内持续的细胞增殖。

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.