Transplacental administration of diethylstilbestrol (DES) causes lesions in female reproductive organs of Donryu rats, including endometrial neoplasia.
The effects of transplacental administration of diethylstilbestrol (DES) on female reproductive organs were investigated using Donryu rats. The animals were given subcutaneous injections of DES dissolved in olive oil at doses of 0.01 or 0.1 mg/kg on days 17 and 19 of gestation. In female offspring, clinical signs, body weights and estrous cycles were continuously assessed until all survivors were killed at month 18. A low mean litter size and shortening of period of pregnancy were recognized in the 0.1 mg/kg group. Disorder and/or suspension of the estrous cycle (so called persistent estrus) also appeared very early in the 0.1 mg/kg group. Macroscopically, the incidences of hypoplasia of the oviduct, cystic dilatation of the uterus and small size of the uterine cervix were higher in the 0.1 mg/kg group than those in the control group. Histologically, in the ovary, the incidence and degree of atrophy were increased in both 0.01 and 0.1 mg/kg groups. In the uterus, total incidences of endometrial hyperplasias were about the same in all groups. However, endometrial adenocarcinomas were dose-dependently increased in the treated groups, the incidence in the 0.1 mg/kg group being significant, compared to that in the control. In the vagina, mucification was more prominent in the treated animals, especially at the higher dose, but no tumors were observed. The present results indicate that prenatal exposure to DES can produce uterine adenocarcinomas in rats, as reported earlier for mice, although its carcinogenic activity is not so strong. Increase of endometrial adenocarcinoma incidence might depend on hormonal imbalance resulting from the ovarian atrophy due to transplacental treatment of DES.
Kitamura
T
T
Toxicology Laboratories, Research and Development Kissei Pharmaceutical Co. Ltd., Nagano, Japan.
Nishimura
S
S
Sasahara
K
K
Yoshida
M
M
Ando
J
J
Takahashi
M
M
Shirai
T
T
Maekawa
A
A
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D004054:Diethylstilbestrol / Q000633:toxicity*; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000473:pathology; D004971:Estrus / Q000187:drug effects; D005187:Fallopian Tubes / Q000187:drug effects / Q000473:pathology; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D008098:Litter Size / Q000187:drug effects; D008297:Male; D008431:Maternal-Fetal Exchange; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D010902:Pituitary Gland / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000187:drug effects / Q000473:pathology
D002273:Carcinogens; D004054:Diethylstilbestrol