Project description:Cadmium is a natural element that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20 Âµg/kg of cadmium chloride and microarray analyses were conducted in the liver and testis 48 hours after injection. Transcriptomics profiles identified in response to cadmium treatment were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testes. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a proposed marker of cadmium exposure, showed a small insignificant increase after 48 hours exposure. Carbohydrate metabolic pathways were also disrupted in cadmium-exposed fish with hepatic transcripts such as UDP-glucose pyrophosphorylase 2 and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signalling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly increased in the liver including genes encoding for the rate limiting steroidogenic acute regulatory protein and the catalytic enzyme 7-dehydrocholesterol reductase. Integration of the transcriptomics data using functional enrichment analyses revealed a number of enriched gene networks associated with previously reported adverse outcomes of cadmium exposure such as liver toxicity and impaired reproduction. Adult largemouth bass (n=4 per treatment) were ip injected with a single dose of cadmium chloride (20 ug/kg) or a saline solution. After 48 hours, liver and testis were excised and differential gene expression profiles were examined.

Project description:Toxaphene (TOX) is an organochlorine pesticide (OCPs) that remains abundant in the environment due to its heavy use in agriculture, its persistence, and its atmospheric transport. In Florida, the north shore of Lake Apopka was heavily used for agriculture decades ago, and TOX remains present in the soil. Wild largemouth bass inhabit the lake, and are potentially exposed to a variety of OCPs. While other OCPs (dieldrin, methoxychlor, p,p’DDE) have been studied for their endocrine disrupting effects in largemouth bass, there are little data available for TOX. Here we performed a 2-month feeding study of male and female largemouth bass with TOX-laced food to mimic the levels found in fish at Lake Apopka. Subsamples of the gonad and liver were collected and preserved in 10% buffered formalin for histopathology and reproductive staging. Plasma levels of vitellogenin (Vtg) testosterone (T) and 17β-estradiol (E2) were quantified and snippets of testis and ovaries were placed into culture to determine ex vivo production of hormones. Lastly, transcriptomics was conducted in both the male testis and liver, as most studies investigating OCPs have analyzed female ovary/liver and data are scarce for OCPs and male bass. Female GSI did not change with TOX but was trending towards a decrease while male GSI did not change with exposure. Female vitellogenin decreased with toxaphene by ~40% but male vitellogenin was not induced. Female and male E2 and T were not different following dietary exposure compared to control bass and this corresponded to ex vivo culture experiments, which revealed no change in E2 and T production from the gonads. Taken together, TOX did not alter the production of E2 and T directly in the gonad tissue. In the testis, transcriptomics revealed that androgen receptor/beta-2-microglobulin signaling was up-regulated while insulin-related pathways were suppressed with TOX. In the liver, the transcriptome analysis revealed an overwhelming suppression in immune-related signaling cascades (e.g. lectin-like receptor and ITSM-Containing Receptor signaling, CD16/CD14 Proinflammatory Monocyte Activation, and CD38/CD3 -> JUN/FOS/NF-kB Signaling in T-cell Proliferation). Ninety percent of the pathways were reduced between 10 to 40% in median network expression. Reduced immune pathways are consistent with other studies investigating OCPs in fish. In the current study, TOX, at the concentrations tested in the diet, did not act as a weak estrogen as many other OCPs do, but rather appeared to be acting as an antiestrogen (or androgen) based upon reduced female Vtg and activation of androgen-receptor mediated pathways in the testis. These data contribute to a comprehensive transcriptomic-physiological framework for TOX and suggests that endocrine disruption may not be the result of direct effects on steroidogenesis in the gonad, but may rather occur at higher levels of the reproductive axis.

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Gene networks and putative toxicity pathways induced by acute exposure to low dose cadmium in largemouth bass (Micropterus salmoides)

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