Differential Estrogen and Antiestrogen Responsiveness of the Uterus During Development in the Fetal, Neonatal and Immature Guinea Pig

Abstract

After 2-day estradiol treatments, wet weight increases in fetuses, newborns and immature guinea pigs by (means .+-. SEM [standard error of the mean]) 75 .+-. 4%, 170 .+-. 16% and 234 .+-. 25%, respectively; while after 3-day tamoxifen treatments they are 83 .+-. 11%, 157 .+-. 35% and 127 .+-. 9%, respectively. During the same periods, estradiol increases the uterine content of DNA while the effect of tamoxifen on uterine DNA decreases throughout development. Histologically, both estradiol and tamoxifen induce in the fetus an increase in the size of the stroma and myometrium. Estradiol or tamoxifen, respectively, increase the luminal epithelial cell height by (means .+-. SEM) 95 .+-. 2% and 67 .+-. 2% in fetuses, 286 .+-. 20% and 100 .+-. 2% in newborns and 260 .+-. 10% and 138 .+-. 4% in immature animals. Luminal epithelial cell number increases in fetuses, newborns and immature animals by (means .+-. SEM) 167 .+-. 10%, 248 .+-. 50% and 76 .+-. 15%, respectively, after estradiol treatments and 160 .+-. 20%, 69 .+-. 15% and 17 .+-. 5%, respectively, after tamoxifen treatments. Uterine epithelial growth invading the stroma was observed in both estradiol- and tamoxifen-treated fetuses. In neonatal or immature animals, estradiol increases the size and the number of endometrial glands, while tamoxifen has progressively less effects on endometrial glands and on the myometrium. The estradiol-induced uterotropic effect increases progressively in fetal, neonatal and immature animals. Throughout development, tamoxifen had progressively weaker estrogenic properties than estradiol. [Prenatal and immediately postnatal treatments with natural estrogens and synthetic estrogenic compounds have been associated with genital tract abnormalities including neoplasia occurring during adulthood in humans and different animal species. Similar long-term abnormalities have also been observed after perinatal administration of triphenylethylene antiestrogens].