Transcriptome Alterations Following Developmental Atrazine Exposure in Zebrafish Are Associated with Disruption of Neuroendocrine and Reproductive System Function, Cell Cycle, and Carcinogenesis
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE117398 | GEO | 2018/07/20
REPOSITORIES: GEO
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Project description:The herbicide atrazine, a suspected endocrine disrupting chemical (EDC), frequently contaminates potable water supplies. Studies suggest alterations in the neuroendocrine system along the hypothalamus-pituitary-gonadal axis; however, most studies address either developmental, pubertal, or adulthood exposures, with few investigations regarding a developmental origins hypothesis. In this study, zebrafish were exposed to 0, 0.3, 3, or 30 parts per billion (ppb) atrazine through embryogenesis and then allowed to mature with no additional chemical exposure. Reproductive function, histopathology, hormone levels, offspring morphology, and the ovarian transcriptome were assessed. Embryonic atrazine exposure resulted in a significant increase in progesterone levels in the 3 and 30 ppb groups. A significant decrease in spawning and a significant increase in follicular atresia in the 30 ppb group were observed. In offspring, a decrease in the head length to body ratio in the 30 ppb group, along with a significant increase in head width to body ratio in the 0.3 and 3 ppb groups occurred. Transcriptomic alterations involved genes associated with endocrine system development and function, tissue development, and behavior. This study provides evidence to support atrazine as an EDC causing reproductive dysfunction and molecular alterations in adults exposed only during embryogenesis and morphological alterations in their offspring.
2016-03-02 | GSE73740 | GEO
Project description:The herbicide atrazine, a suspected endocrine disrupting chemical (EDC), frequently contaminates potable water supplies. Studies suggest alterations in the neuroendocrine system along the hypothalamus-pituitary-gonadal axis; however, most studies address either developmental, pubertal, or adulthood exposures, with few investigations regarding a developmental origins hypothesis. In this study, zebrafish were exposed to 0, 0.3, 3, or 30 parts per billion (ppb) atrazine through embryogenesis and then allowed to mature with no additional chemical exposure. Reproductive function, histopathology, hormone levels, offspring morphology, and the ovarian transcriptome were assessed. Embryonic atrazine exposure resulted in a significant increase in progesterone levels in the 3 and 30 ppb groups. A significant decrease in spawning and a significant increase in follicular atresia in the 30 ppb group were observed. In offspring, a decrease in the head length to body ratio in the 30 ppb group, along with a significant increase in head width to body ratio in the 0.3 and 3 ppb groups occurred. Transcriptomic alterations involved genes associated with endocrine system development and function, tissue development, and behavior. This study provides evidence to support atrazine as an EDC causing reproductive dysfunction and molecular alterations in adults exposed only during embryogenesis and morphological alterations in their offspring. 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 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.
2016-03-02 | E-GEOD-73740 | biostudies-arrayexpress
Project description:The study of epigenetic mechanisms of gene regulation and the role of these mechanisms in developmental reprogramming of the genome and disease susceptibility has increased in recent years. Molecular epigenetic mechanisms regulating gene expression include DNA methylation, histone modifications, and small non-coding RNAs (e.g., microRNAs). MicroRNAs (miRNAs) are short, single-stranded RNA that regulate post-transcriptional control of the translation of mRNA. The importance of these epigenetic regulators in controlling developmental processes is becoming clear. However, to date, few studies have investigated the role of miRNAs in toxicological responses limiting knowledge of these critical regulators in mechanisms of toxicity. Atrazine is a herbicide commonly used throughout the Midwestern United States and other areas of the globe for control of weeds in agricultural crops. In certain areas of the United States, atrazine frequently contaminates potable water supplies above the maximum contaminant level of 3 parts per billion (ppb; mg/L) as set by the United States Environmental Protection Agency (U.S. EPA) and is a suspected endocrine disrupting chemical. Studies have begun to investigate the genetic mechanisms of atrazine toxicity; however, studies investigating epigenetic mechanisms are limited. Here we report that expression of both zebrafish and human miRNAs are significantly altered in response to a developmental atrazine exposure of 0.3, 3, or 30 ppb from 1-72 hours post fertilization (hpf). Altered miRNAs are known to play a role in angiogenesis, cancer, or neuronal development, differentiation, and maturation. Targeted analysis of altered human miRNAs with genes previously identified to be altered by atrazine exposure revealed several targets linked to cell cycle and cell signaling. Further analysis of hsa-miRNA-126-3p which had altered expression in all three atrazine treatments at 72 hpf revealed alterations also occurred at 60 hpf in the 30 ppb treatment group. Results from this study indicate miRNA deregulation in zebrafish and human miRNAs following an embryonic atrazine exposure in zebrafish.
2016-04-21 | GSE78805 | GEO
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.
2016-07-01 | E-GEOD-72243 | biostudies-arrayexpress
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.
2016-07-01 | E-GEOD-72242 | biostudies-arrayexpress
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.
2016-07-01 | GSE72243 | GEO
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.
2016-07-01 | GSE72242 | GEO
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.
2019-12-31 | GSE112503 | GEO
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.
2019-12-31 | GSE112504 | GEO
Project description:Atrazine is an herbicide applied to agricultural crops and is indicated to be an endocrine disruptor. Atrazine is frequently found to contaminate potable water supplies above the maximum contaminant level of 3 mg/L as defined by the U.S. Environmental Protection Agency. The developmental origin of adult disease hypothesis suggests that toxicant exposure during development can increase the risk of certain diseases during adulthood. However, the molecular mechanisms underlying disease progression are still unknown. In this study, zebrafish embryos were exposed to 0, 0.3, 3, or 30 mg/L atrazine throughout embryogenesis. Larvae were then allowed to mature under normal laboratory conditions with no further chemical treatment until 7 days post fertilization (dpf) or adulthood and neurotransmitter analysis completed. No significant alterations in neurotransmitter levels was observed at 7 dpf or in adult males, but a significant decrease in 5-hydroxyindoleacetic acid (5-HIAA) and serotonin turnover was seen in adult female brain tissue. Transcriptomic analysis was completed on adult female brain tissue to identify molecular pathways underlying the observed neurological alterations. Altered expression of 1928, 89, and 435 genes in the females exposed to 0.3, 3, or 30 mg/L atrazine during embryogenesis were identified, respectively. There was a high level of overlap between the biological processes and molecular pathways in which the altered genes were associated. Moreover, a subset of genes was down regulated throughout the serotonergic pathway. These results provide support of the developmental origins of neurological alterations observed in adult female zebrafish exposed to atrazine during embryogenesis.
2018-07-18 | GSE117260 | GEO