ALTERATION OF MAMMARY GLAND DEVELOPMENT AND GENE EXPRESSION BY IN UTERO EXPOSURE TO METALLOESTROGENS
Parodi, Daniela Alida
Early life exposure to estrogens and estrogen like contaminants in the environment are thought to increase the risk of developing breast cancer due to the early onset of puberty in the exposed female. However, the results of this study show that in utero exposure to the metalloestrogen cadmium altered mammary gland development independent of its effect on puberty onset. In utero exposure to the metal resulted in an expansion of the mammary stem and/or progenitor cell population in the neonatal gland and an increase in branching, epithelial cells, and density in the prepubertal gland. Puberty onset resulted in a further expansion of the mammary stem/progenitor cell population and the overexpression of estrogen receptor-alpha that was due to an increase and altered response to estradiol of the transcripts derived from exons O and OT. These results suggest that in utero exposure to cadmium may increase the risk of developing breast cancer by increasing stem/progenitor cell population, density, and estrogen receptor-alpha expression in the mammary gland.
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