Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Embryonic exposure to 10 Âµg/L lead results in female-specific expression changes in genes associated with nervous system development and function and Alzheimerâs disease in aged adult zebrafish brain

ABSTRACT: A developmental lead (Pb) exposure has been proposed as an environmental risk factor for adult neurodegenerative diseases including Alzheimerâs disease (AD). Recent animal studies showed pathological characteristics of AD in adults with a developmental Pb exposure, but additional studies are needed to investigate this phenomenon. To further assess the relationship between an embryonic Pb exposure and latent neurological alterations, the brain of adult female and male zebrafish aged 12 months that were exposed to a control treatment or 10 Âµg/L Pb only during embryogenesis (1- 72 hours after fertilization) were analyzed on a zebrafish-specific microarray platform. Gene ontology and pathway analysis revealed similarities in the top diseases and functional categories in both sexes, but females had 4.3 times more genes altered than males. In addition, alterations in genes associated with nervous system development and function were more pronounced with a set of 89 genes associated with AD including amyloid precursor protein (APP), apolipoprotein (APOE), and sortlin-related receptor precursor (SORL1) observed to be changed in adult females. Our observations suggest that an embryonic exposure to Pb at levels as low as 10 Î¼g/L disturb global gene expression patterns in a sex-specific manner that could lead to neurological alterations in later life. With these findings, future studies investigating the adverse neurological outcomes of these changes in gene expression will facilitate our understanding of the impact of an embryonic 10 Î¼g/L Pb exposure on neurological disease pathogenesis and the inclusion of additional concentrations will broaden our knowledge of dose-dependent changes. A developmental exposure to 10ppb Pb induced global gene expression changes were analyzed in 12 months aged male and female zebarfish brains. A developmental exposure was done shortly after fertilization through 72 hours after fertilization.

ORGANISM(S): Danio rerio

SUBMITTER: Jinyoung Lee

PROVIDER: E-GEOD-74037 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The developmental origins of health and adult disease (DOHaD) hypothesis states that exposure to various environmental stressors early in life can elicit changes to the genome and epigenome thereby resulting in an increased susceptibility of a disease state during adulthood. Atrazine, a common herbicide used throughout the Midwestern United States for control of weeds on various crops frequently contaminates potable water supplies and is a suspected endocrine disrupting chemical. Studies suggest atrazine elicits reproductive dysfunction through the hypothalamus-pituitary-gonadal (HPG) axis. In previous studies, zebrafish were exposed to 0.3, 3, or 30 parts per billion (ppb; ug/L) atrazine through embryogenesis, rinsed, and allowed to mature to adulthood. A decrease in spawning was observed in adults with an embryonic exposure. In addition, adult females had an increase in progesterone and ovarian follicular atresia, alterations in levels of a serotonin metabolite and serotonin turnover in brain tissue, and transcriptome alterations in brain and ovarian tissue supporting neuroendocrine alterations from an embryonic atrazine exposure were reported. Furthermore, offspring of the exposed population exhibited morphological alterations. As reproductive dysfunction may also be influenced by males, this study assessed transcriptomic profiles of brain and testes, morphology, histology, and hormone levels in adult males exposed to atrazine during embryogenesis. Transcriptomic profiles of adult male brain tissue revealed alterations in genes associated with cell to cell signaling and interaction of neurotransmission, cell morphology, cellular assembly and organization of neurites, cellular function and maintenance of neuritogenesis and synaptogenesis, and molecular transport of hormones. In addition, the transcriptomic profiles of adult male testes tissue demonstrated alterations in genes associated with lipid metabolism, molecular transport of steroids, small molecule biochemistry of lipids, and cell morphology. The embryonic atrazine exposure resulted in no alterations in body or testes weight, gonadosomatic index, testes histology, or levels of 11-ketotestosterone or testosterone in adult male zebrafish. Thus, although the transcriptomics data indicate later-in-life alterations on the neuroendocrine system of adult males exposed to atrazine during embryogenesis, analysis of additional endpoints is needed to determine functional impairments. We treated zebrafish embryos from approximately 1 hour post fertilization through 72 hours post fertilization (embryogenesis) to 0, 0.3, 3, or 30 parts per billion (ppb) atrazine. Following the 72 hour exposure period, larvae were rinsed and allowed to mature under normal conditions until adulthood (5-6 months post fertilization). At this time, zebrafish were bred weekly for three weeks in order to initiate breeding cycles. Following this peroid, gonadal tissue was dissected and processed for transcriptomic analysis.

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Embryonic exposure to 10 Âµg/L lead results in female-specific expression changes in genes associated with nervous system development and function and Alzheimerâs disease in aged adult zebrafish brain

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Embryonic exposure to 10 Âµg/L lead results in female-specific expression changes in genes associated with nervous system development and function and Alzheimerâs disease in aged adult zebrafish brain