Distribution of Heavy Metals in the Liver of Foetuses and Female Mice after Oral Administration during Pregnancy - a Histochemical Study

Abstract

The aim of this work was to study the distribution of heavy metals and of subsequently developed morphological changes in the liver of female mice and their foetuses after oral administration of high doses of lead, mercury, and cadmium (0.03 mg of metal per mouse and day). Heavy metals were administered to pregnant female mice on days 9-20 of pregnancy. The animals were euthanised by cervical dislocation. Samples of mother and foetal liver were subsequently collected and processed by means of the common technique for light and electron microscopy. Histochemical reaction based on metal conversion into appropriate sulphide that conjugates with silver was used for detection of heavy metals. Deposits of heavy metals were found at the periphery of lobules of the central vein in the liver of female mice. On the contrary, in the liver of foetuses no predilection site for localisation of the reaction product could be identified. At the electron microscopy level, accumulation of heavy metals was connected as a rule with the occurrence of certain damage to some organelles. Deposits of the reaction product were located mainly in hepatocytes and Kupffer cells. Heavy metals were bound to the heterochromatin of cell nuclei, as well as to some cytoplasmic organelles, such as rough endoplasmic reticulum, mitochondria, ribosomes, and lysosomes. The presence of heavy metals was associated with obliteration of cisternae of the rough endoplasmic reticulum, separation of ribosomes, and destruction of lysosomes. Vacuolation of cell cytoplasm was also a frequent phenomenon. An interesting finding was the "contrasting" of structures containing nucleic acids. Accumulation of metals in the liver of pregnant mice and their foetuses observed in our study indicated that placental barrier does not protect the foetal organism against penetration of metals. Their higher accumulation in foetal compared to maternal liver can be explained by the intense metabolism of differentiating hepatocytes.