Zhang Haolin, Taya Kazuyoshi, Nagaoka Kentaro, Yoshida Midori, Watanabe Gen
Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, PR China; United Graduate School of Veterinarian Science, Gifu University, Gifu 501-1193, Japan; Laboratory of Veterinary Physiology, Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
United Graduate School of Veterinarian Science, Gifu University, Gifu 501-1193, Japan.
Toxicol Lett. 2017 Jul 5;276:92-99. doi: 10.1016/j.toxlet.2017.05.014. Epub 2017 May 15.
Toxic effects induced by exposure to endocrine-disrupting chemicals during fetal and neonatal periods can be irreversible and exert effects throughout an animal's entire life. Our previous study showed that neonatal exposure to 17α-ethynyl estradiol (EE) induced irregular estrous cycle in adults. To uncover the reason for the delayed effect after neonatal exposure to EE, reproductive parameters including ovarian weight, ovarian steroidogenesis, and hormonal profiles were investigated in developing female rats. Ovarian weight decreased at postnatal days (PND) 14 and 21 after neonatal exposure to EE. Ovarian histology at PND21 showed that the ratio of follicles with a diameter >300μm decreased and the ratio of follicles with a diameter of 100-150μm increased in EE-treated ovaries, indicating that neonatal exposure to EE retarded follicular development. Moreover, the expression of P450arom increased at PND14 and the expressions of inhibin/activin subunits βA and βB decreased at PND21 in EE-treated ovaries. Consistent with the expression of P450arom, circulating levels of 17β-estradiol increased at PND14 in EE-treated animals. Furthermore, the circulating levels of luteinizing hormone (LH) also increased at PND14 in the treated animals. Although the expression of Kiss1 did not change in the anteroventral periventricular nucleus (AVPV) of the hypothalamus between controls and EE-treated rats, the expression of Kiss1 was reduced in the arcuate nucleus (ARC) of the hypothalamus at PND14. Based upon those results, we suggest that neonatal exposure to EE disrupted the system regulating the interactions between the reproductive hormones and follicle development in pre-pubertal rats, which may result in reproduction dysfunction in adulthood.
在胎儿期和新生儿期接触内分泌干扰化学物质所引发的毒性作用可能是不可逆的，并会在动物的整个生命周期中产生影响。我们之前的研究表明，新生儿期接触17α-乙炔基雌二醇（EE）会导致成年动物出现不规则的发情周期。为了揭示新生儿期接触EE后出现延迟效应的原因，我们对发育中的雌性大鼠的生殖参数进行了研究，包括卵巢重量、卵巢类固醇生成和激素谱。新生儿期接触EE后，出生后第14天和第21天的卵巢重量下降。出生后第21天的卵巢组织学检查显示，EE处理组卵巢中直径>300μm的卵泡比例下降，直径为100-150μm的卵泡比例增加，这表明新生儿期接触EE会阻碍卵泡发育。此外，EE处理组卵巢在出生后第14天P450arom的表达增加，在出生后第21天抑制素/激活素亚基βA和βB的表达下降。与P450arom的表达一致，EE处理组动物在出生后第14天循环中的17β-雌二醇水平升高。此外，处理组动物在出生后第14天促黄体生成素（LH）的循环水平也升高了。虽然对照组和EE处理组大鼠下丘脑室旁核（AVPV）中Kiss1的表达没有变化，但在出生后第14天，下丘脑弓状核（ARC）中Kiss1的表达降低。基于这些结果，我们认为新生儿期接触EE会破坏青春期前大鼠生殖激素与卵泡发育之间相互作用的调节系统，这可能导致成年期的生殖功能障碍。
