TCDD alters the extracellular matrix and basal lamina of the fetal mouse kidney.
The teratogenic effects of the dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have previously been studied in several species, and hydronephrosis has been reported to be a frequent abnormality in near-term fetuses. C57BL/6N female mice, given 12 micrograms/kg TCDD, P.O., on day 10 of gestation were killed on days 14, 15, and 16; fetal kidneys were collected and prepared for either immunofluorescent localization of several extracellular matrix components (ECM) or transmission electron microscopy (TEM). The TCDD-treated and control kidneys showed the same pattern of staining for fibronectin, but TCDD-treated kidneys displayed a diminished overall intensity. The intensity of laminin and type IV collagen immunofluorescence also appeared to be decreased, and deviations in the pattern of antibody binding were detected for differentiating TCDD-treated nephrons. Binding of the laminin antibody to the basal lamina was decreased in the parietal layer of Bowman's capsules in more advanced stages of differentiation. TEM analysis focused on the basal lamina of the tubules and Bowman's capsule. In TCDD-exposed kidneys, ECM components adjacent to differentiating nephrons were less abundant, and the basal lamina of the developing Bowman's capsules had a diminished lamina densa. The earliest nephrons to develop display these defects and comprise the first functional filtration units of the metanephric kidney. These ultrastructural changes noted in TCDD-exposed nephrons may promote proteinuria, a condition normally observed in the developing kidney when the filtration barrier is immature.
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000648:ultrastructure; D004147:Dioxins / Q000633:toxicity*; D005109:Extracellular Matrix / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D007668:Kidney / Q000002:abnormalities* / Q000187:drug effects / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D013723:Teratogens
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D013723:Teratogens