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Epidemiologic studies and animal studies increasingly suggest that exposures to environmental chemicals, nutrition, physical factors, and other factors early in development have a role in susceptibility to disease in later life. The mammalian female reproductive system arises from the uniform paramesonephric duct, the müllerian duct. The major subtypes of epithelial ovarian cancer (EOC) show morphologic features that resemble those of the müllerian duct-derived epithelia of the reproductive tract. Exposure of the developing female reproductive tract to diethylstilbestrol (DES), either in vivo or in organ culture, repressed the expression of HOXA10 in the uterus and resulted in uterine metaplasia. Epigenetic change in the molecular program of cell differentiation in the affected tissues may be a common mechanism. Most regions of the mammalian genome exhibit little variability among individuals in tissue-specific DNA methylation levels. Future analyses of epigenetic imprints of genes explain the developmental origins of disease.
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