Project description:According to the developmental origins of health and disease (DOHaD) hypothesis, exposure to environmental stressors during early development can cause genetic, epigenetic, or functional changes in tissues that increase disease risk later in life. Atrazine (ATZ) is a commonly used pesticide that frequently contaminates rural and urban water sources at levels above the 3 ppb maximum contaminant level set by the US Environmental Protection Agency. Exposure to ATZ is linked to endocrine disruption, cancer, changes in genome methylation, and alterations in neurochemistry and behavior. This study tests the hypothesis that embryonic exposure to ATZ results in sex-specific changes in behavior, the adult brain transcriptome, and adult body and brain pathology, according to the DOHaD hypothesis. Zebrafish (Danio rerio) embryos were exposed to 0, 0.3, 3, or 30 ppb (ppb; µg/L) ATZ during the period from fertilization through 72 hours post fertilization (hpf), and then were rinsed and raised to maturity with no further exposure. At 9 months post fertilization (mpf), a novel tank test, a light-dark box, and an open field test evaluated adult behavior. Transcriptomic analysis investigated ATZ related differences in gene expression and the brain was evaluated histopathologically for morphometric alterations in the area of the dorsal telencephalon, posterior tuberculum, and raphe populations. At 14 mpf, the body length, weight, and brain weight was measured to evaluate effects of ATZ on mature body and brain size. The 9 mpf adult behavioral tests found non-monotonic, sex-specific behavior changes, with male zebrafish having decreased activity and female zebrafish having increased signs of anxiety. Transcriptomic analysis identified sex-specific alterations, with females having altered expression of genes in pathways related to cancer and organismal injury and males having altered gene expression in organismal development and reproductive system development and function pathways. Morphometric analysis identified a decreased number of cells in male raphe populations and adult zebrafish also had non-monotonic, sex-specific alterations in body length, body weight, and brain weight. This results suggests that developmental exposure to ATZ does cause sex-specific alterations in adult neural function.

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.

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, larave 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 disseceted and processed for transcriptomic analysis.

Dataset Information

Embryonic Atrazine Exposure Causes Behavioral, Transcriptomic, Epigenetic, and Pathological Alterations in Adult Zebrafish Brain

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