ABSTRACT. The aim of this study was to investigate the effect of exposure period and dose of diethylstilbestrol (DES), which has strong estrogenic activity, on pregnancy in rats. All rats with observed vaginal plugs or sperm in vaginal smear tests after mating were divided into 3 groups: those fed a normal diet, a diet mixed with DES throughout pregnancy and a diet mixed with DES from day 13 of pregnancy. DES was mixed into the diet at 0.1, 1, 10 and 100 ppm. All bred rats fed the normal diet and 0.1 ppm DES from day 13 of pregnancy delivered pups, while none of the rats treated with 1-100 ppm DES during pregnancy and 100 ppm DES from day 13 of pregnancy delivered any pups. The number of male and female pups born decreased in rats treated with 10 ppm DES from day 13 of pregnancy. These results suggest that DES could affect pregnancy and that the exposure period and dose may result in sterility, abortion, poor fetal growth and reduced number of pups born.KEY WORDS: diethylstilbestrol (DES), lactation, pregnancy, rat.J. Vet. Med. Sci. 71 (10): [1309][1310][1311][1312][1313][1314][1315] 2009 There is evidence that many environmental endocrine disruptors act as sex hormones, particularly during the perinatal or neonatal period, directly or indirectly affecting reproduction in human and rats [14,21,23]. Endogenous hormone mimics have been proposed for a number of adverse human health effects, including infertility, abnormal prenatal and childhood development and reproductive cancers [18].In humans, women exposed to diethylstilbestrol (DES), a synthetic estrogen with strong estrogenic activity, during pregnancy have a moderately increased risk of breast cancer [17,23]. It is also known that the frequency of vaginal clear cell adenocarcinoma is increased in young women whose mothers used DES to prevent or lower the risk of abortion [4,23]; women had taken the DES tablets at 50-200 mg/day during pregnancy [1]. However, DES is ineffective in prevention of miscarriages and premature births [4,23]. DES has also been used as a good model reagent for investigation pre-or post-natal effects of estrogenic compounds on females using animal models for human extrapolation.We have previously reported that neonatal administration of DES induced persistent estrus and an absence of corpus lutea in female rats due to disturbance of the gonadotropinsecreting system in the hypothalamus [11,16,24]. However, it remains to be determined whether the administration of DES affects pregnancy in rats.In this study, doses of 0.1 to 100 ppm DES were selected because daily gavages with DES at 90 mg/kg/day during pregnancy result in high prenatal fetal mortality in rats [2]. The period after major organogenesis also selected for examination of DES, from day 13 of pregnancy, because the period of major organogenesis in rats is from day 6 to day 15 of pregnancy [8]; in particular, development of mammary hillocks occurs on day 13 of pregnancy [20]. Therefore, the pregnant rats were fed a diet containing 0.1 to 100 ppm DES during the entire pregnanc...