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Effects of prepubertal exposure to forchlorfenuron through prenatal and postnatal gavage administration in developing Sprague-Dawley rats
Reproductive Toxicology ( IF 3.3 ) Pub Date : 2020-09-28 , DOI: 10.1016/j.reprotox.2020.09.009
Difeng Zhu 1 , Li Ping 1 , Xiaofei Shen 1 , Yawen Hong 1 , Qinjie Weng 1 , Qiaojun He 1 , Jiajia Wang 1 , Jincheng Wang 1
Affiliation  

Forchlorfenuron (CPPU), a plant growth regulator, is widely used in agriculture. However, its long-term exposure effects on humans, especially neonates, remain unclear. Therefore, we investigated the developmental toxicity of prenatal and postnatal gavage administration of CPPU in rats. Pregnant Sprague-Dawley rats were administered 300 mg/kg/day CPPU by gavage from day 6 of gestation to the cessation of nursing. During weaning, rat offspring were administered 0, 30, 100, or 300 mg/kg/day CPPU for 4 weeks, followed by a 4-week CPPU-free recovery period. There were no significant differences in clinical symptoms, body weight, development indicators, serum biochemical parameters, sex hormone levels, sperm motility, relative organ weights, and histopathological changes among the 0–100 mg/kg/day CPPU groups. In the 300 mg/kg/day CPPU group, female rats exhibited decreased body weight, earlier time of vaginal opening (VO) and first estrus time (FE), elevated estradiol and blood urea nitrogen (BUN) levels, and upregulation of estrogen receptor 1 gene expression, whereas male rats only exhibited increases in serum BUN, creatinine, and glucose levels. Most changes were reversed after the recovery period. Furthermore, the endometrial epithelial height was significantly increased in female rats despite the absence of significant changes in uterine wall thickness and endometrial glands. Thus, CPPU may promote estradiol secretion, resulting in altered VO and FE and adverse effects in prepubertal female rats. These findings may be applied for risk assessment following CPPU exposure in humans.



中文翻译:

Sprague-Dawley 大鼠通过产前和产后灌胃给药青春期前暴露于氯苯脲的影响

氯苯脲 (CPPU) 是一种植物生长调节剂,广泛用于农业。然而,其对人类,尤其是新生儿的长期暴露影响仍不清楚。因此,我们研究了大鼠产前和产后强饲 CPPU 的发育毒性。从妊娠第 6 天到停止哺乳,通过管饲法向怀孕的 Sprague-Dawley 大鼠施用 300 mg/kg/天的 CPPU。在断奶期间,给大鼠后代施用 0、30、100 或 300 mg/kg/天 CPPU,持续 4 周,然后是 4 周的无 CPPU 恢复期。0-100 mg/kg/day CPPU组在临床症状、体重、发育指标、血清生化指标、性激素水平、精子活力、相对器官重量和组织病理学变化方面没有显着差异。在 300 mg/kg/天 CPPU 组中,雌性大鼠表现出体重减轻、阴道开口时间 (VO) 和首次发情时间 (FE) 提前、雌二醇和血尿素氮 (BUN) 水平升高以及雌激素受体 1 基因表达上调,而雄性大鼠仅表现出增加血清 BUN、肌酐和葡萄糖水平。大多数变化在恢复期后被逆转。此外,尽管子宫壁厚度和子宫内膜腺体没有显着变化,但雌性大鼠的子宫内膜上皮高度显着增加。因此,CPPU 可能会促进雌二醇分泌,导致青春期前雌性大鼠的 VO 和 FE 改变以及不良反应。这些发现可用于人类接触 CPPU 后的风险评估。雌二醇和血尿素氮 (BUN) 水平升高,雌激素受体 1 基因表达上调,而雄性大鼠仅表现出血清 BUN、肌酐和葡萄糖水平升高。大多数变化在恢复期后被逆转。此外,尽管子宫壁厚度和子宫内膜腺体没有显着变化,但雌性大鼠的子宫内膜上皮高度显着增加。因此,CPPU 可能会促进雌二醇分泌,导致青春期前雌性大鼠的 VO 和 FE 改变以及不良反应。这些发现可用于人类接触 CPPU 后的风险评估。雌二醇和血尿素氮 (BUN) 水平升高,雌激素受体 1 基因表达上调,而雄性大鼠仅表现出血清 BUN、肌酐和葡萄糖水平升高。大多数变化在恢复期后被逆转。此外,尽管子宫壁厚度和子宫内膜腺体没有显着变化,但雌性大鼠的子宫内膜上皮高度显着增加。因此,CPPU 可能会促进雌二醇分泌,导致青春期前雌性大鼠的 VO 和 FE 改变以及不良反应。这些发现可用于人类接触 CPPU 后的风险评估。大多数变化在恢复期后被逆转。此外,尽管子宫壁厚度和子宫内膜腺体没有显着变化,但雌性大鼠的子宫内膜上皮高度显着增加。因此,CPPU 可能会促进雌二醇分泌,导致青春期前雌性大鼠的 VO 和 FE 改变以及不良反应。这些发现可用于人类接触 CPPU 后的风险评估。大多数变化在恢复期后被逆转。此外,尽管子宫壁厚度和子宫内膜腺体没有显着变化,但雌性大鼠的子宫内膜上皮高度显着增加。因此,CPPU 可能会促进雌二醇分泌,导致青春期前雌性大鼠的 VO 和 FE 改变以及不良反应。这些发现可用于人类接触 CPPU 后的风险评估。

更新日期:2020-09-28
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