Gene expression profiles in the brain of the neonate mouse perinatally exposed to methylmercury and/or polychlorinated biphenyls

Abstract

Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are environmentally persistent neurodevelopmental toxicants. The primary source of human exposure is the consumption of contaminated fish, seafood and marine mammals. However, little is known about the molecular mechanisms of MeHg and PCB toxicities and interactions between these contaminants. We investigated the functional profiles of differently expressed genes in the brains of offspring mice perinatally exposed to MeHg and/or PCBs to elucidate how these contaminants interact with each other. Pregnant mice (C57BL/6) were divided into four groups by exposure: (1) vehicle control, (2) MeHg alone, (3) PCBs alone, (4) MeHg + PCBs. Gene expression analysis of the brains of offspring mice was carried out with 4 x 44 K whole mouse genome's microarrays (Agilent) on postnatal day 1. The gene expression pattern of the MeHg exposure-group differed from that of the PCB-exposure group. The MeHg + PCB group expressed a larger number of genes, most of which were not expressed in the MeHg group or PCB group. It was revealed that gene expression was greatly increased, and the most altered genes were found with co-exposure. The genes were related to the functional categories of development, inflammation, calcium ion homeostasis, signal transduction, the ubiquitin-proteasome pathway and detoxication. The ubiquitin-proteasome system and detoxication categories might function for protection against the toxicity induced by co-exposure to MeHg and PCBs. These results suggest that co-exposure does not simply exacerbate the toxicity of MeHg alone or PCB alone, but stimulates a protection system.

Cerebral gene expression in response to single or combined gestational exposure to methylmercury and selenium through the maternal diet

“…The reason for this is unclear. A recent study by Shimada et al (2010) found that the concurrent exposure of MeHg with polychlorinated biphenyls also induced a much larger number of significant changes in gene expression than exposure to the individual components alone. The gene expression response to the concurrent exposure of MeHg and Se in the current investigation may reflect effects related to the strong affinity between MeHg and Se that would not be apparent when each is dosed independently.…”

Transgenerational neuroendocrine disruption of reproduction

“…Together, these findings show that PCBs interfere with DNA methylation machinery in the rat. Finally, numerous studies have shown that PCBs can have long-term effects on gene expression after developmental exposure, 77,78 providing evidence that epigenetic mechanisms may be involved in the persistent effects of perinatal PCB exposure.…”

Race and the new epigenetic biopolitics of environmental health

“…Recent studies are further explicating the mechanisms, finding that methylmercury not only causes cell death but affects cell division and neuronal stem cell differentiation (Johansson et al, 2007;Castoldi et al, 2008). On the basis of studies of rodents, researchers are finding that methylmercury, alone and in combination with other environmental chemicals such as PCBs, regulates gene expression in both neuronal and glial cells; and it does so through several pathways, including DNA methylation, histone modification and mRNA expression (Onishchenko et al, 2008;Padhi et al, 2008;Desaulniers et al, 2009;Glover et al, 2009;Hogberg et al, 2010;Shimada et al, 2010). Thus, although the evidence remains quite new and focused on mice and rats, it appears that methylmercury affects the cellular environment in ways that epigenetically regulate gene expression.…”