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

Abstract

Controversy remains regarding the safety of consuming certain types of seafood, particularly during pregnancy. While seafood is rich in vital nutrients, it may also be an important source of environmental contaminants such as methylmercury (MeHg). Selenium (Se) is one essential element present in seafood, hypothesised to ameliorate MeHg toxicity. The aim of the present study was to ascertain the impact of Se on MeHg-induced cerebral gene expression in a mammalian model. Microarray analysis was performed on brain tissue from 15-day-old mice that had been exposed to MeHg throughout development via the maternal diet. The results from the microarray analysis were validated using qPCR. The exposure groups included: MeHg alone (2.6 mg kg−1), Se alone (1.3 mg kg−1), and MeHg + Se. MeHg was presented in a cysteinate form, and Se as Se–methionine, one of the elemental species occurring naturally in seafood. Eight genes responded to Se exposure alone, five were specific to MeHg, and 63 were regulated under the concurrent exposure of MeHg and Se. Significantly enriched functional classes relating to the immune system and cell adhesion were identified, highlighting potential ameliorating mechanisms of Se on MeHg toxicity. Key developmental genes, such as Wnt3 and Sparcl1, were also identified as putative ameliorative targets. This study, utilising environmentally realistic forms of toxicants, delivered through the natural route of exposure, in association with the power of transcriptomics, highlights significant novel information regarding putative pathways of selenium and MeHg interaction in the mammalian brain.Electronic supplementary materialThe online version of this article (doi:10.1007/s10565-010-9180-4) contains supplementary material, which is available to authorized users.

Characterizing the Low-Dose Effects of Methylmercury on the Early Stages of Embryo Development Using Cultured Human Embryonic Stem Cells

“…In the present study, we observed floating cells every day, even in the control group before the daily medium change, and the number of floating cells was higher in wells with cells that had been treated with MeHg. This effect of MeHg treatment on cell adhesion has also been reported previously ( Jayashankar et al. 2011 ).…”

Sex-specific transcriptional responses of the zebrafish (Danio rerio) brain selenoproteome to acute sodium selenite supplementation

“…To our knowledge, only two studies have investigated the transcriptomic response of the brain to dietary Se with microarray technologies (6,54). These studies, however, were not designed to ascertain the molecular influence of Se in the brain under normal physiological conditions of Se sufficiency.…”

“…The other was chiefly concerned with the protective role of Se in preventing neurotoxicity from methyl mercury exposure. However, as a control, the study measured the global transcriptional response of the brain in BALB/c mice pups gestationally exposed to dietary selenomethionine supplementation (54). A substantial transcriptional response was observed in the cere- bral cortex of male mice from a Se-deficient to supplemented status (17% of the genes represented on the array were differentially expressed) (6).…”

Mechanisms and modifiers of methylmercury-induced neurotoxicity

“…Experimental studies have shown that Se supplementation attenuates growth and motor deficits in rats chronically exposed to MeHg following weaning, the severity of deficits was not directly related to MeHg levels in the brain but rather by the Hg:Se ratio 103 In 15-day-old mice born to dams fed MeHg with or without Se supplementation through gestation and lactation, combined Se and MeHg regulated expression of 63 genes in whole genome cerebral microarray compared to 8 and 5 genes affected by Se or MeHg alone, respectively 104 . This is consistent with a functional Se deficiency resulting from MeHg inhibition of selenoproteins, effects that can be lessened by Se supplementation 105 .…”