The transplacental toxicity of methyl mercury to fetal rat liver mitochondria. Morphometric and biochemical studies.
Ultrastructural morphometric and biochemical changes in liver mitochondria of fetal rats whose mothers were exposed to methyl mercury hydroxide in their drinking water at concentrations of 0, 3, 5, or 10 p.p.m. for 4 weeks prior to mating and through day 19 of pregnancy are described. A dose-related decrease in the volume density of mitochondria was observed in fetal hepatocytes of dams given the 5- and 10-p.p.m. dose levels. This finding was associated with decreased mitochondrial protein synthesis, which appeared to result primarily from decreased synthesis of mitochondrial structural proteins. Loss of respiratory control was observed in mitochondria from animals in the 3-p.p.m. dose group whereas state 3 respiration was abolished in animals exposed to the 5- and 10-p.p.m. dose levels. The specific activities of monoamine oxidase and cytochrome oxidase, outer and inner mitochondrial membrane marker enzymes respectively, showed dose-related decreases of up to 62 and 78 per cent of control, respectively. delta-Aminolevulinic acid synthetase, which is loosely bound to the inner mitochondrial membrane, also showed dose-related decreases of up to 68 per cent of control. Malate dehydrogenase, a mitochondrial matrix marker enzyme, showed no change in activity at any dose level tested. These observations were correlated with dose-related tissue concentrations of methyl and inormpaired mitochondrial biogenesis and functional development is one basis for explaining the sensitivity of fetal animals to methyl mercury toxicity.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000479:Alkylmercury Compounds / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D008099:Liver / Q000648:ultrastructure; D008291:Malate Dehydrogenase / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D008995:Monoamine Oxidase / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D013997:Time Factors
D000479:Alkylmercury Compounds; D008291:Malate Dehydrogenase; D008995:Monoamine Oxidase; D003576:Electron Transport Complex IV; D000624:5-Aminolevulinate Synthetase