首页> 外文期刊>The Journal of toxicological sciences >Early indicators of delayed adverse effects in female reproductive organs in rats receiving neonatal exposure to 17alpha-ethynylestradiol
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Early indicators of delayed adverse effects in female reproductive organs in rats receiving neonatal exposure to 17alpha-ethynylestradiol

机译:新生儿暴露于17α-乙炔雌二醇的大鼠雌性生殖器官不良反应延迟的早期指标

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We previously reported that neonatal exposure to 17a-ethynylestradiol (EE) led to delayed adverse effects in which age-related anovulation after sexual maturation was accelerated. To identify early indicators of these adverse effects, female Wistar Hannover GALAS rats received a single EE injection (0, 0.02, 0.2, 2, 20, or 200 ug/kg) within 24 hr of birth. Histopathological changes in ovarian and uterine development were investigated from postnatal day (PND) 14 to 10 weeks of age. Immunohisto-chemical expression of estrogen receptor alpha (ERa) in the uterus, serum levels of sex-related hormones and gene expression in the hypothalamus were examined. Although neonatal exposure to EE did not affect body growth or ovarian development, serum FSH tended to decrease at doses > 2 ug/kg, and Kiss1 mRNA level in the whole hypothalamus was significantly decreased in all EE-treated groups at PND14. The number of uterine glands at PND21 was suppressed at doses > 20 ug/kg, and ERa expression in the uterine epithelium at estrus stage decreased in a dose-dependent manner at 10 weeks of age. These results demonstrated that the various identified changes that occurred before the appearance of delayed adverse effects could be candidate early indicators.
机译:我们先前曾报道新生儿暴露于17a-乙炔雌二醇(EE)会导致不良反应延迟,其中性成熟后与年龄有关的无排卵现象会加速。为了确定这些不良反应的早期指标,雌性Wistar Hannover GALAS大鼠在出生后24小时内接受了一次EE注射(0、0.02、0.2、2、20或200 ug / kg)。从出生后的第14天到10周龄(PND),研究卵巢和子宫发育的组织病理学变化。检查子宫内雌激素受体α(ERa)的免疫组织化学表达,性相关激素的血清水平和下丘脑的基因表达。尽管新生儿暴露于EE不会影响人体生长或卵巢发育,但在PND14时,所有EE治疗组的血清FSH倾向于在> 2 ug / kg剂量时降低,整个下丘脑的Kiss1 mRNA水平显着降低。剂量> 20 ug / kg时,PND21处的子宫腺数量受到抑制,发情期子宫上皮中的ERa表达在10周龄时呈剂量依赖性降低。这些结果表明,在延迟不良反应出现之前发生的各种确定的变化可能是早期候选指标。

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