TCDD-induced hyperplasia of the ureteral epithelium produces hydronephrosis in murine fetuses.

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) has been recognized as a kidney and palate teratogen for many years. The etiology of the kidney abnormality has not been revealed, and there is some confusion about the exact nature of the defect. This study examines C57BL/6N fetal mouse kidneys from day 14 of gestation through day 17. Pregnant females received a single dose of 0 or 12 micrograms TCDD/kg by gavage on day 10 pregnancy. Fetal urinary systems were examined on days 14, 15, 16 (a.m.), 16 (p.m.), and 17 (p.m.). The patency of the ureteric lumen was examined by injection of dye into the bladder. TCDD treatment did not delay or prevent breakdown of the ureteric membrane between days 15 and 16. On days 16 through 17, the ureteric lumina of TCDD-exposed fetuses were narrow and tortuous when compared to the control lumens. Sections of ureter were observed by light microscopy. On day 15 the lumina of TCDD-exposed ureters were occluded by epithelial cells. As a result of hyperplasia of the ureteric luminal epithelium, hydroureter and hydronephrosis became pronounced by day 17. We conclude that the kidney abnormality induced by TCDD is true hydronephrosis, which is defined as the accumulation of urine in the kidney due to obstructed outflow.