Effects of acute and chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin on the transition to reproductive senescence in female Sprague-Dawley rats
Effects of acute and chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin on the transition to reproductive senescence in female Sprague-Dawley rats
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DOI：
10.1095/biolreprod.105.044396
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发表时间：
2006-01-01
影响因子：
3.6
通讯作者：
Petroff, BK
中科院分区：
文献类型：
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作者：
Franczak, A;Nynca, A;Petroff, BK
芳香烃受体(AHR)的激活可以发生在受污染的环境中，要么来自与吸烟有关的毒物，要么来自内源性配体。我们测试了急性或长期暴露于AHR激动剂2，3，7，8-四氯二苯并-对二恶英(TCDD)是否改变了雌性SD大鼠向生殖衰老的转变。在实验1中，大鼠(n=6)灌胃给予TCDD 0或10 mg/kg(P.O.)在出生后第29天。每月监测阴道细胞学1wk，直到1岁时处死大鼠。单次暴露于青春期前的TCDD可加速雌性大鼠向生殖衰老的过渡，并与青春期延迟、周期性异常和生殖早衰有关。在第二个实验中，大鼠从子宫开始，通过每周给药(0，50或200 ng kg(-1)wk 1，n=7)，慢性暴露于TCDD。终生接触这些较低剂量的TCDD会导致正常周期性的剂量和时间依赖性丧失，并显著加速向生殖衰老过渡的开始(P<；0.05)。这种向生殖衰老的过早转变与发情周期延长有关，在TCDD的最高剂量下，持续发情或间情期。TCDD不改变卵泡的数量和大小。长期接触TCDD的大鼠的黄体生成素浓度与对照组相似，而孕酮在两种剂量的二恶英中都有升高的趋势(P<；0.08)。TCDD染毒50 ng/kg组小鼠血清FSH水平升高(P<；0.02)。而雌二醇在两个剂量的二恶英中均降低(P<；0.01)。到目前为止，数据支持内分泌中断而不是耗尽卵泡储备是TCDD激活AHR途径后雌性大鼠过早过渡到生殖衰老的主要机制。
Activation of the aryl hydrocarbon receptor (AHR) can occur in polluted environments, either from smoking-related toxicants or from endogenous ligands. We tested whether acute or chronic exposure to the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters the transition to reproductive senescence in female Sprague-Dawley rats. In experiment 1, rats (n = 6 per experimental group) received a single dose of 0 or 10 mu g/kg of TCDD orally (p.o.) on Postnatal Day 29. Vaginal cytology was monitored for 1 wk each month until rats were killed at 1 yr of age. The single prepubertal exposure to TCDD hastened the transition to reproductive senescence in female rats and was associated with delayed puberty, abnormal cyclicity, and premature reproductive senescence. In a second experiment, rats were exposed to TCDD chronically through weekly dosing (0, 50, or 200 ng kg(-1) wk 1 p.o., n = 7 each dose beginning in utero. Lifelong exposure to these lower doses of TCDD induced a dose- and time-dependent loss of normal cyclicity and significantly hastened the onset of the transition to reproductive senescence (P < 0.05). This premature transition to reproductive senescence was associated with prolonged estrous cycles and, at the highest dose of TCDD, persistent estrus or diestrus. The number and size of ovarian follicles were not altered by TCDD. Diestrous concentrations of LH in rats exposed chronically to TCDD were similar to those in controls, whereas progesterone tended to be elevated at both doses of the dioxin (P < 0.08). Serum FSH was elevated in the group exposed to 50 ng/kg of TCDD (P < 0.02). whereas estradiol was decreased at both doses of dioxin (P < 0.01). Data thus far support endocrine disruption rather than depletion of follicular reserves as a primary mechanism of the premature transition to reproductive senescence following activation of the AHR pathway by TCDD in female rats.