Kato Hideo, Ota Takao, Furuhashi Tadakazu, Ohta Yasuhiko, Iguchi Taisen
Nihon Bioresearch Inc., 6-104 Majima, Fukujyu-cho, Hashima, Gifu, 501-6251, Japan.
Reprod Toxicol. 2003 May-Jun;17(3):283-8. doi: 10.1016/s0890-6238(03)00002-9.
The effects of neonatal administration of estrogenic agents on rat reproductive organs were examined. Either bisphenol A (BPA; 0.25, 1, or 4mg/pup) or 10 micro g 17beta-estradiol (E(2)) was given subcutaneously to Sprague-Dawley female rats during the neonatal period from post-natal day (PND) 0 to 9. Animals ovariectomized at 80 days were given subcutaneous injections of 1 micro g/kg E(2) for 3 days from PND 94 to 96. Clefts in the clitoris, early vaginal opening, irregular estrous cycles, a decrease in the area occupied by the corpora lutea (CL) in the ovary, and multiple cystic follicles in the ovary were found in the animals treated neonatally with 1mg BPA. Uterine fluid weight measured after E(2) treatment on PND 94-96 was less than controls. In addition to these abnormalities, unusual body weight gains, persistent vaginal cornification, and lack of CL were observed in females treated neonatally with 4mg BPA. The ovary weight on PND 80 and uterine fluid weight measured after E(2) treatment on PND 94-96 were less than controls for the 4mg BPA group. Neonatal treatment with 10 micro g E(2) induced similar abnormalities as found in the 4mg BPA group. These results show that BPA when given during the neonatal period caused changes in female reproductive organs.
研究了新生大鼠给予雌激素制剂对其生殖器官的影响。在出生后第(PND)0至9天的新生期,给Sprague-Dawley雌性大鼠皮下注射双酚A(BPA;0.25、1或4mg/只幼崽)或10μg 17β-雌二醇(E₂)。80日龄时进行卵巢切除的动物,在PND 94至96期间皮下注射1μg/kg E₂,持续3天。在新生期用1mg BPA处理的动物中,发现阴蒂出现裂隙、阴道开口提前、发情周期不规则、卵巢中黄体(CL)所占面积减小以及卵巢中出现多个囊性卵泡。在PND 94 - 96进行E₂处理后测量的子宫液重量低于对照组。除了这些异常外,在新生期用4mg BPA处理的雌性动物中还观察到体重异常增加、持续性阴道角化以及缺乏黄体。对于4mg BPA组,PND 80时的卵巢重量以及在PND 94 - 96进行E₂处理后测量的子宫液重量均低于对照组。新生期用10μg E₂处理诱导出与4mg BPA组类似的异常。这些结果表明,新生期给予BPA会导致雌性生殖器官发生变化。