Department of Toxicology, Slovak Medical University, Bratislava, Slovak Republic.
Toxicol Mech Methods. 2011 Jun;21(5):406-17. doi: 10.3109/15376516.2010.551554. Epub 2011 Feb 15.
The purpose of this study was to evaluate the effects of neonatal exposure to the herbicide acetochlor (ACT) on pubertal development and reproductive functions in female Wistar rats and to investigate capability of ACT to interfere with estradiol binding to rat uterine estrogen receptors (ERs) ex vivo.
Acetochlor (7.68 and 15.36 mg/kg/day) was administered by subcutaneous injection from postnatal day (PND) 4-7, and vaginal opening, and estrous cyclicity were evaluated from PND 8-159. A second group of adult ovariectomized female rats was dosed for 6 days with ACT (153.6 mg/kg/day, oral gavage). The interference of ACT with the binding of [³H]Estradiol -17β to uterine nuclear and cytoplasmic estrogen receptors was analyzed ex vivo in receptor binding assay.
Both doses of ACT caused acceleration of the age at eye opening and vaginal patency that were significantly different from the control. In addition, altered estrous cyclicity was observed in the ACT (15.36 mg/kg/day) group with 54% of the female rats displaying irregular cycles at PND 159. While uterine weights were not altered, a significant accumulation of uterine nuclear estrogen receptors was observed in the ACT group.
These results indicate that acetochlor can act as the endocrine disruptor and that endpoints related to pubertal development and reproductive functions sensitive sites are targeted with this persistent pollutant.
本研究旨在评估除草剂乙草胺(ACT)对雌性 Wistar 大鼠青春期发育和生殖功能的影响,并研究 ACT 对雌二醇与大鼠子宫雌激素受体(ER)体外结合的干扰能力。
从出生后第 4-7 天开始,通过皮下注射给予乙草胺(7.68 和 15.36mg/kg/天),从第 8-159 天评估阴道开口和动情周期。第二组成年去卵巢雌性大鼠连续 6 天经口灌胃给予 ACT(153.6mg/kg/天)。在受体结合测定中分析 ACT 对[³H]雌二醇-17β与子宫核和细胞质雌激素受体结合的干扰。
两种剂量的 ACT 均导致眼睛睁开和阴道开放的年龄提前,与对照组相比有显著差异。此外,在 ACT(15.36mg/kg/天)组中观察到动情周期发生改变,54%的雌性大鼠在第 159 天出现不规则周期。虽然子宫重量没有改变,但 ACT 组子宫核雌激素受体明显积累。
这些结果表明乙草胺可以作为内分泌干扰物,并且该持久性污染物靶向青春期发育和生殖功能敏感的终点。