Effect of neonatal DES exposure on the mouse uterus

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Quantitative and cell-type-specific expression of c-fos and c-jun genes after 17β-estradiol (E2) stimulation, was investigated in the uteri of adult ovariectomized and 3-week-old immature mice, which were neonatally exposed to diethylstilbestrol (DES)(DES-mice) or vehicle (control-mice), employing Northern blot analysis, immunohistochemistry and in situ hybridization.Both adult ovariectomized and immature mice showed almost the same c-fos and c-jun expression pattern, respectively. The c-fos mRNA level before E2 injection (at baseline) was higher in the DES-mice than in controls. The c-fos mRNA level reached to a peak at 2 hours after E2 injection in both DES-and control mice. However, the c-fos mRNA level in the DES-mice was much lower than that in the control. Most uterine epithelia of DES-mice revealed low sensitivity to the c-fos expression after E2 administration compared with those of controls, whereas few epithelia showed high c-fos mRNA expression even at baseline. The c-jun mRNA level in the uteri of DES-mice at baseline was slightly lower than in that of controls. After 1 to 2 hours of E2 injection, c-jun mRNA levels increased. There were no significant differences in the distribution pattern of c-jun protein and mRNA in the uteri of DES-and control mice ; E2 stimulated c-jun expression in the stromal and myometrial cells but suppressed it in the epithelial cells. The permanent changes in the expression of estrogen-regulated protooncogenes, c-fos and c-jun genes, by neonatal DES exposure may be responsible for the wide range of abnormalities in the genital tract of mature animals.