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

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine-disrupting chemical that alters cellular organization 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 proliferation and apoptosis in a manner that may enhance disease, including carcinogenesis.

TCDD inhibits spontaneous differentiation in human embryonic stem cells

“…Though effects of TCDD on cellular differentiation have been shown to vary based on tissue type and species [7], the inhibitory effect of TCDD on the process of epithelial to mesenchymal transition (EMT) in rodent palatal development has been well described [9,10]. Genital malformations such as cleft clitoris and incomplete vaginal openings, as well as delayed maturation of mammary and uterine tissue have also been described, further suggesting an inhibitory effect of TCDD on cellular differentiation and early developmental processes in rodent models [11][12][13].…”