These studies were performed to investigate the effects of MeHg on testicular function in Macaca fascicularis monkeys. In an in vivo study involving oral treatment of adult males Macaca fascicularis monkeys with MeHg for 20 weeks, changes in spermatozoal production, motility and morphology and in serum testosterone were followed before, during and after treatment. MeHg treatment significantly decreased % motile spermatozoa and scores for sperm speed and forward progression and increased % abnormal sperm tail forms, at sub-neurotoxic levels. The MeHg-induced increase in semen abnormalities was not accompanied by any significant changes in serum levels of testosterone. No consistent histological abnormalities were detected in testicular biopsies from the treated animals at the end of the treatment period. A good recovery pattern was observed for the MeHg effects on sperm motility while this was unclear for the effects on sperm morphology.

Infant crab-eating macaques exposed in utero to maternal subclinical levels of methylmercury (MeHg) and their nonexposed controls were administered an adaptation of a standardized test of visual recognition memory. Exposed animals showed recognition deficits in that they directed significantly less visual attention to novel stimuli than did controls. These results parallel those obtained by other investigators with high-risk and teratogen-exposed human infants.

were further categorized into the percentages of phagocytic PAM's containing one (27 percent), two (15 percent), three (11 percent), four (8 percent), five (7 percent), and more than five (32 percent) spheres. The average percentage of cells with one or more spheres measured on 41 normal rats was 28.2 ± 8.2 percent.Since this percentage was lower than anticipated, we designed experiments to determine if all macrophages in the alveolar region were being exposed to spheres and if the spheres were in high enough concentration. Rats were again instilled in vivo with green fluorescent spheres for 2 hours. Samples were washed to remove nonphagocytized spheres and then incubated in vitro for 30 minutes with red fluorescent spheres 1.65 ,um in diameter (7). Microscopic examination showed that 35 percent of the PAM's had both red and green spheres, more than 60 percent contained only red spheres, and less than 5 percent had no spheres. Thus there were PAM's within the lungs that had not phagocytized green spheres but were capable of phagocytizing red spheres in vitro. These results suggested that the instillation of 1 x 107 to 2 x 107 spheres was insufficient to distribute them to all macrophages within the lungs. To alleviate this problem, we killed the rats, surgically exposed the trachea, opened the thoracic cavity, and instilled 15 ml of green fluorescent spheres (5 x I0 per milliliter) into the lungs hydrostatically (25 cm H20) by way of the trachea. After 30 minutes the lungs were lavaged and the percentage of phagocytic cells was quantitated microscopically and by FCM analysis. The results showed that more than 90 percent of the cells were phagocytic.Finally, to determine if microspheres were being phagocytized or instead were being nonspecifically bound to the cell surface, rat PAM's were exposed in vitro to 0, 0.1, 0.3, and 1.0 percent sodium azide and green fluorescent spheres. Experimental FCM data showed ( Table 1) that 91 percent of PAM's that were not exposed to sodium azide had associated spheres, whereas only 6 to 7 percent had spheres associated with them when exposed to 0.3 to 1.0 percent sodium azide. The microscopically determined phagocytoses were within 5 percent of the FCM results. Decreased phagocytosis, induced by sodium azide, was also shown in terms of a reduction in the number of particles per cell. Thus, as determined by FCM, the percentage of PAM's containing one to five spheres increased, whereas the percentage con-taining more than five spheres decreased. These data show that, as the inhibitor concentration increased, the percentage of phagocytic PAM's decreased and those PAM's that were phagocytic had fewer spheres.Although Sprague-Dawley rats were used in these studies, results may differ among rat strains and animal species. Since the microspheres contain surface carboxyl groups, they can be coated with opsonins, antibodies, or other chemicals for studying specific receptor-mediated phagocytosis (8). This technology has broad application for the rapid and accurate determination of phagoc...

The disposition parameters derived from a compartmental model kinetic analysis of blood Hg levels in nonpregnant, adult female Macaca fascicularis given daily doses of MeHg did not vary with either dosage level (50, 70 or 90 micrograms MeHg/kg b.wt.day) or duration of exposure (up to 507 day). In contrast, blood clearance of Hg in pregnant females was dose-dependent; it being higher at the 90 micrograms MeHg/kg b.wt.day than at the lower dosage levels. Hg levels in the brain of adult fascicularis relative to blood Hg also increased at the highest level of exposure. Blood Hg half-life in neonate fascicularis was similar to half-life in their mothers (adults). Finally, the regional distribution of mercury in the brains of adult and neonate fascicularis exposed to low and intermediate levels of MeHg resembles the reported distribution of mercury in the brains of adult and neonate humans environmentally exposed to MeHg. Consequently, M. fascicularis may be an especially appropriate animal model for studying the neurotoxic mechanisms of chronic methyl mercury exposure.

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