Project description:This study sought to evaluate the effects of dietary MeHg exposure on adult female yellow perch (Perca flavescens) and zebrafish (Danio rerio) reproduction by relating controlled exposures with subsequent reproductive effects. Yellow perch were used in the study for their socioeconomic and ecological importance within the Great Lakes basin, and the use of zebrafish allowed for a detailed analysis of the molecular effects of MeHg. MeHg exposures at environmentally relevant levels were done in zebrafish for a full life cycle, mimicking a realistic exposure scenario, and in adult yellow perch for twenty weeks, capturing early seasonal ovarian development. In zebrafish, several genes involved in reproductive processes were shown to be dysregulated by RNA-seq and QPCR, but no significant phenotypic or physiological changes were observed with ovarian staging, fecundity, or embryo mortality. Yellow perch did not appear to be affected by MeHg, either at a molecular level, as assessed by QPCR of eight genes in the pituitary, liver, and ovary tissue, or a physiological level, as seen with ovarian somatic index, circulating estradiol, and ovarian staging. Lack of impact in yellow perch limits the usefulness of zebrafish as a model and suggests that the reproductive sensitivity to environmentally relevant levels of MeHg differs between yellow perch and zebrafish.
Project description:Methylmercury (MeHg) is an environmental neurotoxicant known to cause adverse effects in fish, such as locomotor abnormalities, visual deficits or teratogenesis. However, very few studies have investigated the effects of environmentally realistic MeHg exposures on the gene expression of fish embryos. Since the primary source of MeHg exposure in wild fish is through the diet, this study analyzed differential gene expression in zebrafish embryos from parents that had been subjected to environmentally relevant dietary MeHg exposures (0, 1, 3, and 10ppm) throughout their whole life cycle.
Project description:Rationale: Dieldrin is a legacy organochlorine pesticide that is persistent in the environment, despite being discontinued from use in North America since the 1970s. Some epidemiological studies suggest that exposure to dieldrin is associated with increased risks of neurodegenerative disease and breast cancer by inducing inflammatory responses in tissues as well as oxidative stress. However, the direct effects of organochlorine pesticides on the heart have not been addressed adequately to date. This is a significant knowledge gap because these chemicals are detectable in human serum and are environmentally persistent, thus individuals may show latent adverse effects due to chronic, low dose exposure over time. Objective: To determine whether low level exposure to dieldrin at an environmentally relevant dose results in aberrant molecular signaling in the vertebrate heart. Methods and Results: Using transcriptomic profiling and immunoblotting, we determined the global gene and targeted protein expression response to dieldrin treatment, and show that dieldrin effects gene regulator networks in the heart that are associated with protein degradation. Our results show that genes related to the development of cardiovascular disease, specifically cardiac arrest and ventricular fibrillation, are affected by environmentally relevant levels of dieldrin. We find that genes regulating inflammatory responses, a significant risk factor for cardiovascular disease, are upregulated by dieldrin treatments. Transcripts related to lysosomal function, also important to heart function, are significantly downregulated. To verify these findings, proteins in these pathways were examined with immunoblotting, and our data suggest that dieldrin constitutively activates Akt/mTOR signalling and downregulates lysosomal genes, which is hypothesized to be mediated through Transcription Factor EB (TFEB), the master regulator of lysosome function. Conclusions: This study is one of few to report that dieldrin alters molecular signaling cascades in the cardiovascular system and proposes a novel mechanism for pesticide-induced cardiotoxicity.