Tetracycline-induced changes in hepatocytes of mini-pigs and mini-pig foetuses as revealed by electron microscopy

The effect of chlortetracycline on hepatocytes from pregnant mini-pigs and their half-term foetuses was studied after oral administration of 1-3 g daily for 6 days. Liver tissue from tetracycline-treated mini-pigs and their foetuses was immersion fixed, and hepatocytes were evaluated by qualitative and quantitative electron microscopy and compared to hepatocytes of untreated controls. After exposure to tetracycline the hepatocytes of the pregnant mini-pig showed a significant increase in the volume density of mitochondria and autophagic vacuoles. Also a significant decrease in the volume density of glycogen was observed. The hepatocytes of the tetracycline-exposed half-term foetuses showed profound morphological changes of mitochondria. Many mitochondria were of an abnormal shape and an increased size. In most mitochondria the matrix contained a paracrystalline material which had a characteristic prismatic shape with a regular internal lattice structure. Many mitochondria also exhibited numerous short stacked cristae or long longitudinally oriented cristae. No significant change in the volume density of mitochondria was demonstrated. Also no significant change in the volume density of glycogen was observed. In conclusion it can be stated that small doses of chlortetracycline administered orally for a few days provoke morphological changes in both maternal and foetal hepatocytes. While the changes in maternal hepatocytes may reflect metabolic changes, the distinct morphological changes of mitochondria in foetal hepatocytes probably indicate cellular injury.