Zhu Difeng, Ping Li, Shen Xiaofei, Hong Yawen, Weng Qinjie, He Qiaojun, Wang Jiajia, Wang Jincheng
Center for Drug Safety Evaluation and Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Center for Drug Safety Evaluation and Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Reprod Toxicol. 2020 Dec;98:157-164. doi: 10.1016/j.reprotox.2020.09.009. Epub 2020 Sep 28.
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.
氯吡脲（CPPU）是一种植物生长调节剂，在农业中广泛使用。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，我们研究了产前和产后经口灌胃给予大鼠氯吡脲的发育毒性。将怀孕的Sprague-Dawley大鼠从妊娠第6天至停止哺乳期间经口灌胃给予300mg/kg/天的氯吡脲。在断奶期间，给大鼠后代分别给予0、30、100或300mg/kg/天的氯吡脲，持续4周，随后是4周的无氯吡脲恢复期。在0-100mg/kg/天的氯吡脲组中，临床症状、体重、发育指标、血清生化参数、性激素水平、精子活力、相对器官重量和组织病理学变化均无显著差异。在300mg/kg/天的氯吡脲组中，雌性大鼠体重下降、阴道开口（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血清BUN、肌酐和葡萄糖水平升高。恢复期后，大多数变化得以逆转。此外，尽管子宫壁厚度和子宫内膜腺体无显著变化，但雌性大鼠的子宫内膜上皮高度显著增加。因此，氯吡脲可能促进雌二醇分泌，导致VO和FE改变，并对青春期前雌性大鼠产生不良影响。这些发现可用于评估人类暴露于氯吡脲后的风险。
