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Effects of Prenatal Methylmercury Poisoning Upon Growth and Development of Fetal Central Nervous System

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Reproductive and Developmental Toxicity of Metals

Abstract

Analysis of neuropathological findings in human infants poisoned by maternal ingestion of methylmercury-contaminated food during pregnancy reveals that the principal histopathologic changes are represented by the outcome of disturbance in brain development, more specifically abnormal neuronal migration, deranged cortical differentiation and exuberant white matter astrocytosis. Although these changes are by no means specific, the striking similarity of the pathologic anatoiriy of the brain of all infants reported in Japan and Iraq and the detailed account of clinical and toxicological data is highly suggestive of a common pathogenetic link to methylmercury poisoning in utero. Thus, the critical periods of vulnerability of developing CNS for sublethal exposure to methylmercury appear to be the late embryonic and fetal periods when neuronal migration and histogenetic development of brain are taking place actively. In order to test this hypothesis, experimental studies using cultures of human fetal brain cells were carried out. Using time-lapse cinematography, phase and electron microscopy and immunocytochemistry, we have been able to observe the cessation of migratory activity of cultured human fetal neurons and astrocytes due to cytotoxic actions of methylmercury. Methylmercury not only caused rapid disruption and degeneration of membranes but also caused specific damage to microtubules in neurons and astrocytes in culture. We have also demonstrated inhibitory effect of methylmercury on DNA synthesis of human fetal astrocytes by radioautography and showed beneficial effect of meso–2,3- dimercaptosuccinic acid on methylmercury-damaged human fetal astrocytes by time-lapse cinematography. Studies of developing mouse brain revealed significant reduction in dendritic arborization of neurons (Jacobson, 1978)• However, there are still many uncertainties regarding the time of origin of different types of neurons and glial cells in various regions of the developing human CNS. Contrary to the general belief that neuronal development precedes glial development (Fujita, 1963, 1967), our studies (Choi, 1981) and those of others (Levitt et al., 1980, 1981) suggest the likelihood of concomitant generation of both types of cells in the early developing human embryo. Until these and other uncertainties regarding neurogenesis are resolved, therefore, it will be difficult to ascertain precisely the molecular mechanisms and stages of development that are applicable to methylmercury poisoning in utero.

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  1. Division of Neuropathology, Department of Pathology, California College of Medicine University of California, Irvine, California, USA

    Ben H. Choi

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  1. Ben H. Choi
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  1. Division of Toxicology Department of Radiation Biology and Biophysics, University of Rochester School of Medicine, Rochester, New York, USA

    Thomas W. Clarkson  & Polly R. Sager  & 

  2. Department of Environmental Medicine, University of Umea, Umea, Sweden

    Gunnar F. Nordberg

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Choi, B.H. (1983). Effects of Prenatal Methylmercury Poisoning Upon Growth and Development of Fetal Central Nervous System. In: Clarkson, T.W., Nordberg, G.F., Sager, P.R. (eds) Reproductive and Developmental Toxicity of Metals. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9346-1_21

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