In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in the C57BL/6J mouse prostate: lobe-specific effects on branching morphogenesis

Abstract

Branching morphogenesis is an essential component of prostate development. This study was conducted to test the hypothesis that in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure differentially inhibits branching morphogenesis and ductal canalization in the ventral, dorsal, lateral, and anterior mouse prostate. Pregnant C57BL/6J mice were given TCDD (5 microg/kg, orally) or vehicle on gestation day (GD) 13 and their pups examined at 1, 7, 14, 21, 35, and 90 days of age. Prostate lobes were microdissected after incubation in 0.5% collagenase and the numbers of ductal tips, main ducts, and ductal tips per main duct were determined by examining photographs of microdissected, whole-mount specimens. Ductal canalization was determined using histological sections of the dorsolateral and anterior prostate lobes. TCDD inhibited branching morphogenesis in all prostate lobes. The ventral prostate (VP) was extremely small throughout development and never developed any ductal structure. TCDD reduced the numbers of ductal tips and main ducts in the dorsal (DP) and lateral prostate (LP), but reductions in ductal tip numbers appeared to result entirely from reductions in the number of main ducts. Dorsolateral prostate (DLP) weights were slightly reduced by TCDD, but there was no effect on ductal canalization in the dorsal, lateral, or anterior lobes. TCDD had no effect on main duct number in the anterior prostate, but weight, ductal tip number, and the number of ductal tips per main duct was substantially reduced. These results demonstrate that the severe inhibition in ventral prostate development caused by in utero and lactational TCDD exposure is accompanied by a complete absence of branching morphogenesis. The impairment in dorsal, lateral, and anterior prostate (AP) development is associated with a lobe-specific inhibition of the various processes involved in duct formation.