Henry E C, Miller R K, Baggs R B
Teratology. 1984 Apr;29(2):297-304. doi: 10.1002/tera.1420290216.
The synthetic estrogen, diethylstilbestrol (DES), causes urogenital malformations in humans, primates, and rodents. This study was designed to determine whether these effects of DES are related to its estrogenicity. Therefore, DES (0.1, 1, and 10 micrograms) or the natural estrogen, estradiol (E2) (10 and 100 micrograms) was injected directly into day 19 rat fetuses. In the 6- to 7-week-old female offspring exposed to DES, a dose-related incidence of cleft phallus, hypospadias, and incomplete coiling of oviducts was observed. The single fetal injection of E2 elicited similar urogenital malformations, but was approximately 100-fold less potent than DES. A single subcutaneous dose of either DES (0.025, 0.25, or 2.5 mg/kg) or E2 (2.5 or 25 mg/kg) to dams on day 19 of pregnancy induced a spectrum of malformations similar to that following fetal injection. The offspring of treated dams, but not those injected directly as fetuses, had nonfunctioning ovaries (no corpora lutea) yet vaginal signs of estrous were present. It is concluded that DES can act directly in the fetus and its teratogenicity does not require maternal mediation. Since a high dose of E2 produced similar malformations when given to fetuses, it appears that excess estrogen during prenatal life is teratogenic. Thus, at least those endpoints of the teratogenicity of DES that were measured are accounted for by its estrogenic activity.
合成雌激素己烯雌酚（DES）可导致人类、灵长类动物和啮齿动物出现泌尿生殖系统畸形。本研究旨在确定DES的这些作用是否与其雌激素活性有关。因此，将DES（0.1、1和10微克）或天然雌激素雌二醇（E2）（10和100微克）直接注射到妊娠第19天的大鼠胎儿体内。在暴露于DES的6至7周龄雌性后代中，观察到阴茎裂、尿道下裂和输卵管不完全卷曲的发生率与剂量相关。单次给胎儿注射E2也引发了类似的泌尿生殖系统畸形，但效力约为DES的1/100。在妊娠第19天给孕鼠单次皮下注射DES（0.025、0.25或2.5毫克/千克）或E2（2.5或25毫克/千克），诱发的一系列畸形与胎儿注射后的情况相似。接受处理的孕鼠后代，而非直接作为胎儿注射的后代，卵巢无功能（无黄体），但有发情期的阴道表现。得出的结论是，DES可直接作用于胎儿，其致畸性不需要母体介导。由于给胎儿注射高剂量E2时会产生类似的畸形，似乎产前过量雌激素具有致畸性。因此，至少所测量的DES致畸性的那些终点是由其雌激素活性所致。
