Prenatal TCDD Exposure Delays Differentiation and Alters Cell Proliferation and Apoptosis in the Uterus of the Sprague-Dawley Rat

Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine-disrupting chemical that alters cellular organiza- tion at both macroscopic and molecular levels. Our goal was to determine the effects that prenatal TCDD exposure has on uterine morphology, cell proliferation, apoptosis, and protein expression. Pregnant Sprague-Dawley rats were treated with 3 μg TCDD/kg body weight by gavage on gestational day 15. At 50 days postpartum, female offspring exposed in utero to TCDD displayed uteri that were atrophic in appearance, but with a 2-fold significant increase in luminal epithelial cell proliferation and a significant decrease in apoptosis (10- and 4-fold in glandular and luminal epithelium, respectively), compared to the controls. Epidermal growth factor receptor (EGFR) was significantly increased and superoxide dismutase 1 (SOD1) was significantly decreased in uteri of rats exposed prenatally to TCDD. We conclude that TCDD can inhibit maturation and modulate uterine proteins that are known to play a role in uterine growth as well as alter epithelial cell pro- liferation and apoptosis in a manner that may enhance disease, including carcinogenesis.