Experimental Approaches to Developmental Toxicity of Methylmercury

  • Minoru Inouye
Part of the Rochester Series on Environmental Toxicity book series (RSET)


Dozens of babies congenitally affected by methylmercury were born in Minamata, Japan and Iraq. For the most severe cases, where death occurred either in infancy or in childhood, pathological examinations were performed. In cases from Iraq the changes in the brains were the outcome of disturbances of development, more specifically, abnormal neuronal migration and derangement in the fundamental structuring of gray matter. The focal nerve cell destruction typically seen in adult cases of methylmercury poisoning was not encountered (Choi et al., 1978). In cases from Minamata, on the other hand, brain changes were the result of degeneration and decrease in the number of nerve cells. These findings were similar in type to those found in adult patients, and in addition were accompanied by developmental changes (Matsumoto et al., 1965).

Our experiment using guinea pigs demonstrated that developmental disturbances of the brain as a result of impaired neurogenesis and abnormal neuronal migration were induced when dams were exposed to methylmercury in early pregnancy. When dams were exposed in later pregnancy, neurons of the cerebral cortex were involved in widespread focal degeneration. These findings confirmed and extended the observations of the human cases. Iraqi cases were affected acutely in the earlier stage of pregnancy, so the fetal brain might be involved in developmental disturbances. The Minamata cases were exposed to methylmercury chronically throughout the pregnancy, and thus both the developmental disturbances and the focal degeneration of neurons might be induced in the same fetal brain. Accelerated placental transfer and fetal accumulation of methylmercury at the late pregnant stage, as demonstrated in animal experiments, might cause the degenerative changes of neurons resembling the adult forms.

In addition, hydrocephalus has been detected with a low incidence in congenital Minamata disease sufferers. Experimental studies using inbred mice revealed strain difference in susceptibility to postnatal development of hydrocephalus following prenatal methylmercury exposure. B10.D2 is highly susceptible, C57BL/10 and C57BL/6 are moderately susceptible, and DBA/2, C3H/He and BALB/c are resistant. This indicates that the susceptibility to methylmercury-induced hydrocephalus is under genetic control.


Fetal Brain Placental Transfer Developmental Toxicity Minamata Disease Developmental Disturbance 
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Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Minoru Inouye
    • 1
  1. 1.Research Institute of Environmental MedicineNagoya UniversityNagoyaJapan

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