Diethylstilbestrol-induced perinatal lethality in the rat. II. Perturbation of parturition.
Evidence is presented suggesting that the fetolethal properties of diethylstilbestrol (DES) are indirect, mediated maternally through a perturbation of the normal mechanisms of parturition. Oral administration of the compound to Sprague-Dawley rats near Day 18 of pregnancy was shown to delay the onset of parturition, prolong labor, and induce dystocia, with a concomitant large increase in perinatal mortality. Exposure during Days 8-16 was without effect, whereas treatment in the Day 18-20 interval resulted in preterm delivery. Inability to initiate labor at term, accompanied by fetal death, also resulted from the administration of hCG on Days 16-18. The relative incidence of stillbirths in DES-exposed pups was markedly decreased by Caesarean delivery. The average weight of the maternal pituitary gland was not affected by treatment, whereas maternal adrenal glands were 30% larger. Maternal blood levels of corticosterone were not significantly elevated, however. The average number of follicles on Day 21 was significantly reduced by DES, and a histological analysis failed to demonstrate a luteotropic effect of the compound. In dams treated on Days 8-18, serum progesterone was reduced by as much as 60%, and total estrogens were 32% lower than in controls. We conclude that DES acts in the rat to depress the preterm levels of steroid hormones, which leads to a failure of uterine contraction accompanied by placental detachment and fetal death.
Zimmerman
S A
SA
Department of Zoology, Brigham Young University, Provo, Utah 84602.
Clevenger
W R
WR
Brimhall
B B
BB
Bradshaw
W S
WS
D000818:Animals; D000831:Animals, Newborn; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced*; D005865:Gestational Age; D006728:Hormones / Q000097:blood; D007743:Labor, Obstetric / Q000187:drug effects* / Q000502:physiology; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D006063:Chorionic Gonadotropin; D006728:Hormones; D004054:Diethylstilbestrol