Burroughs C D, Bern H A, Stokstad E L
J Toxicol Environ Health. 1985;15(1):51-61. doi: 10.1080/15287398509530635.
This study used the neonatal mouse model to determine if early exposure of female mice to coumestrol, a plant estrogen, would result in reproductive-tract alterations similar to those seen after neonatal exposure to diethylstilbestrol (DES). Newborn female C57BL/Crgl mice were given daily subcutaneous injections of 0.08 micrograms DES or 100 micrograms coumestrol in 0.005 ml dimethyl sulfoxide (DMSO), or DMSO alone, or were untreated, for the first 5 d of life. The doses chosen were equivalent in biological activity based on published uterine bioassay data (using young adult mice). Observations were made twice daily for 1.5 mo to determine the times of eye and complete vaginal opening. Half of the animals were ovariectomized at 40 d of age. Vaginal lavages were examined for 30 consecutive d beginning both at 2 and at 5 mo of age. DES and coumestrol significantly advanced the time of complete vaginal opening and induced a comparable degree of ovary-independent persistent vaginal cornification. In addition, coumestrol resulted in the occurrence of hemorrhagic ovarian follicles.
本研究采用新生小鼠模型，以确定雌性小鼠在新生期接触植物雌激素香豆雌酚后，是否会出现与新生期接触己烯雌酚（DES）后类似的生殖道改变。新生雌性C57BL/Crgl小鼠在出生后的前5天，每天皮下注射0.08微克DES或100微克香豆雌酚（溶于0.005毫升二甲基亚砜（DMSO）中），或仅注射DMSO，或不进行处理。根据已发表的子宫生物测定数据（使用成年小鼠），所选用的剂量在生物活性上是等效的。每天观察两次，持续1.5个月，以确定睁眼和完全阴道开口的时间。一半的动物在40日龄时进行卵巢切除。分别在2月龄和5月龄时开始连续30天检查阴道灌洗液。DES和香豆雌酚显著提前了完全阴道开口的时间，并诱导了相当程度的不依赖卵巢的持续性阴道角化。此外，香豆雌酚导致了出血性卵巢卵泡的出现。
