Effects of exposure period and dose of diethylstilbestrol on pregnancy in rats.

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.

[1]  V. Beral,et al.  Randomised trial of high doses of stilboestrol and ethisterone therapy in pregnancy: long-term follow-up of the children. , 1981, Journal of epidemiology and community health.

[2]  R. Hoover,et al.  Prenatal Diethylstilbestrol Exposure and Risk of Breast Cancer , 2006, Cancer Epidemiology Biomarkers & Prevention.

[3]  S. Lightman,et al.  Habituation and Cross‐Sensitization of Stress‐Induced Hypothalamic‐Pituitary‐Adrenal Activity: Effect of Lesions in the Paraventricular Nucleus of the Thalamus or Bed Nuclei of the Stria Terminalis , 2002, Journal of neuroendocrinology.

[4]  H. Yoshida,et al.  Effects of neonatally-administered 17beta-estradiol on induction of mammary carcinomas by 7, 12-dimethylbenz[a]anthracene in female rats. , 2006, In Vivo.

[5]  J. Vondráček,et al.  Estrogenic activity of environmental polycyclic aromatic hydrocarbons in uterus of immature Wistar rats. , 2008, Toxicology letters.

[6]  G. Saggese,et al.  High incidence of central precocious puberty in a bounded geographic area of northwest Tuscany: An estrogen disrupter epidemic? , 2005, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[7]  E. Pirog,et al.  The Female Genital Tract , 2010 .

[8]  C. O'neill,et al.  Elevated luteal phase estradiol:progesterone ratio in mice causes implantation failure by creating a uterine environment that suppresses embryonic metabolism. , 1990, Fertility and sterility.

[9]  W. Bradshaw,et al.  Diethylstilbestrol-induced perinatal lethality in the rat. I. Relationship to reduced maternal weight gain. , 1991, Biology of reproduction.

[10]  D. L. Greenman,et al.  Comparison of histological responses of BALB/c and B6C3F1 female mice to estradiol when fed purified or natural-ingredient diets. , 1986, Journal of Toxicology and Environmental Health, Part A.

[11]  H. Yoshida,et al.  Effects of neonatally administered low-dose diethylstilbestrol on the induction of mammary carcinomas and dysplasias induced by 7,12-dimethylbenz [a] anthracene in female rats. , 2008, In vivo.

[12]  L. Gosselin,et al.  Effects of ovariectomy and estrogen on skeletal muscle function in growing rats , 2004, Journal of Muscle Research & Cell Motility.

[13]  S. Safe.  Clinical correlates of environmental endocrine disruptors , 2005, Trends in Endocrinology & Metabolism.

[14]  H. Yoshida,et al.  Effects of Neonatally Administered Diethylstilbestrol on Induction of Mammary Carcinomas Induced by 7, 12-Dimethylbenz[A]Anthracene in Female Rats , 2007, Toxicologic pathology.

[15]  L. Johnson,et al.  Effects of dietary 17 beta-estradiol exposure on serum hormone concentrations and testicular parameters in male Crl:CD BR rats. , 1998, Toxicological sciences : an official journal of the Society of Toxicology.

[16]  J. Russo,et al.  Morphology and Development of the Rat Mammary Gland , 1989 .

[17]  H. Kawaguchi,et al.  Effects of 4-n-Octylphenol on the Induction of Mammary Tumors Induced by 7,12-Dimethylbenz[a]anthracene in Rats , 2009, Veterinary pathology.

[18]  H. Kawaguchi,et al.  Effects of Neonatally Administered High-dose Diethylstilbestrol on the Induction of Mammary Tumors Induced by 7,12-Dimethylbenz[a]anthracene in Female Rats , 2009, Veterinary pathology.

[19]  K. P. Phillips,et al.  Key Developments in Endocrine Disrupter Research and Human Health , 2008, Journal of toxicology and environmental health. Part B, Critical reviews.

[20]  J. Reeves,et al.  Pituitary and ovarian luteinizing hormone releasing hormone receptors during the estrous cycle, pregnancy and lactation in the rat. , 1982, Biology of reproduction.

[21]  F. A. Smith,et al.  Vinyl chloride: inhalation teratology study in mice, rats and rabbits. , 1981, Environmental health perspectives.

[22]  D. Williams.  The female genital tract and urethra , 1958 .

[23]  H. Yoshida,et al.  Effects of High Doses of 17β-estradiol and Ovariectomy on 7, 12-Dimethylbenz[a]anthracene-Induced Mammary Carcinomas and Dysplasias in Neonatally Androgenized Female Sprague-Dawley Rats , 2000 .

[24]  M. Koster,et al.  The History of DES, Lessons to be Learned , 2005, Pharmacy World and Science.