Role of placental metallothionein in maternal to fetal transfer of cadmium in genetically altered mice.
The role of placental metallothionein (MT) as a barrier for maternal to fetal transfer of cadmium (Cd) was investigated using mice which overexpressed the MT-1 isoform (MT-1*), mice which did not express the MT-1 and 2 isoforms (MT-null) and control mice (C57BL/6). In addition, immunohistochemical localization of MT in the placenta was determined in these mice. Two days prior to parturition, the mice were injected with radioactive 109Cd chloride (4 microCi, 0.6 ng Cd/mouse) and killed 24 h later. Organs and fetuses were collected and radioactivity, MT and metal levels were measured. Cd accumulated mainly in the liver and kidney (80% of administered dose) with very low levels (0.1-0.3%) detected in fetuses. When analyzed on a per organ or per gram basis, MT-null fetuses accumulated significantly more Cd (3-10-fold) than the control fetuses and there was no significant difference in fetal Cd accumulation in the MT-1* and control fetuses. As expected, MT and zinc levels were higher in MT-1* than C57BL/6 mice and no MT was detected in MT-null mice. Most striking was the high hepatic MT levels in MT-1* dams (4 mg/g). Immunohistochemical analysis showed MT staining in spongiotrophoblasts, glycogen cells, visceral yolk sac, trophoblast giant cells and maternal decidual cells with the MT-1* placenta staining much more intensely as compared to control placenta. The results suggest that placental MT reduces maternal to fetal Cd transfer, however the low doses of Cd administered in the present experiment resulted in high levels of Cd accumulation in liver and kidney in all groups of mice with a low concentration of Cd reaching the placenta. Thus, the role of placental MT as a barrier for Cd is inconclusive.
Department of Pathology, University of Western Ontario, London, Canada.
J C
JC
Lau
M G
MG
Joseph
M G
MG
Cherian
D000818:Animals; D001692:Biological Transport; D002104:Cadmium / Q000378:metabolism* / Q000493:pharmacokinetics; D002106:Cadmium Radioisotopes; D002850:Chromatography, Gel; D003300:Copper / Q000032:analysis; D005260:Female; D005333:Fetus / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D014599:Uterus / Q000378:metabolism; D015032:Zinc / Q000032:analysis
D002106:Cadmium Radioisotopes; D002104:Cadmium; D003300:Copper; D008668:Metallothionein; D015032:Zinc