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Effect of neonatal DES exposure on the mouse uterus

新生儿 DES 暴露对小鼠子宫的影响

基本信息

批准号：
11670030
负责人：
YAMASHITA Shuji
金额：
$ 2.3万
依托单位：
Keio Junior College of Nursing
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

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.

用17β-雌二醇（E2）刺激成年去卵巢小鼠和3周龄未成熟小鼠子宫，观察子宫内c-fos和c-jun基因的定量表达和细胞类型特异性表达。（DES-小鼠）或溶剂（对照小鼠），采用北方印迹分析，成年卵巢切除小鼠和未成熟小鼠分别显示几乎相同的c-fos和c-jun表达模式。DES小鼠注射E2前（基线）的c-fos mRNA水平高于对照组。DES组和对照组c-fos mRNA表达均在注射E2后2 h达到高峰。而DES小鼠的c-fos mRNA水平明显低于对照组。与对照组相比，大多数DES小鼠子宫上皮对E2给药后c-fos表达的敏感性较低，而即使在基线时，也很少有上皮显示出高c-fos mRNA表达。DES小鼠子宫中c-jun mRNA水平在基线时略低于对照组。注射E2后1 ~ 2 h，c-jun mRNA水平升高。DES和对照小鼠子宫中c-jun蛋白和mRNA的分布模式无显著差异; E2刺激间质和子宫肌层细胞中c-jun的表达，但抑制上皮细胞中的c-jun表达。雌激素调节的原癌基因，c-fos和c-jun基因的表达的永久性变化，新生儿DES暴露可能是负责在成熟动物的生殖道的广泛的异常。