Transcriptomics analysis and hormonal changes of female and male rats treated chronically with a low dose of acrylamide in their water supply
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Reyna Colli-Dula
PROVIDER: E-GEOD-62026 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Acrylamide is a type-2 alkene monomer with established human neurotoxic effects. While the primary source of human exposure to acrylamide is occupational, other exposure sources include food, drinking water, and smoking. In this study, neurobehavioral assays coupled with transcriptional profiling analysis were conducted to assess both behavioral and gene expression effects induced by acrylamide neurotoxicity in rats when administered during early postnatal life. Acrylamide administration in rat pups induced significant characteristic neurotoxic symptoms including increased heel splay, decrease in grip strength, and decrease in locomotor activity. Transcriptome analysis with the Affymetrix Rat Genome 230 2.0 array indicated that acrylamide treatment caused a significant alteration in the expression of genes involved in muscle contraction, pain regulation, and dopaminergic neuronal pathways. First, in agreement with the observed behavioral effects, expression of the Mylpf gene involved in muscle contraction was downregulated in the spinal cord in response to acrylamide. Second, in sciatic nerves, acrylamide repressed the expression of the opioid receptor gene Oprk1 that is known to play a role in neuropathic pain regulation. Finally, in the cerebellum, acrylamide treatment caused a decrease in the expression of the nuclear receptor gene Nr4a2 that is required for development of dopaminergic neurons. Thus, our work examining the effect of acrylamide at the whole-genome level on a developmental mammalian model has identified novel genes previously not implicated in acrylamide neurotoxicity that can be further developed into biomarkers for assessing the risk of acrylamide exposure. Three-week-old male Wistar rat pups were treated with either acrylamide or saline daily (30 mg/kg) for 21 days, then tissues (cerebellum, spinal cord, and sciatic nerve) were harvested and frozen. Two biological replicate samples, each sample consisting of pooled tissue from 2 rats, were analyzed for each treatment.
2012-02-08 | E-GEOD-29004 | biostudies-arrayexpress
Project description:New mechanisms-of-action of anthocyanins (ACNs) provided by a red-fleshed apple compared with a white-fleshed apple ACN-poor, and with an ACN-rich extract on the proteome profile of aorta and heart as cardiovascular key tissues were determined. Hypercholesterolemic Wistar rats were separated into the corresponding groups to analyze the proteomic profile of the aorta and heart tissues using nano-liquid chromatography coupled to mass-spectrometry. Red-fleshed apple downregulated CRP, C1QB and CFP related-inflammation. White-fleshed apple reduced C1QB, CFB, CFD, C3, and C9 related to the complement system, reduced MB and CP related to iron metabolism, and increased ME1, PKM, and PC related to energy homeostasis. ACN-rich extract increased FMOD, TAGLN, and CAP1 related to cellular structure and decreased PRKACA, IQGAP1, and HSP90AB1 related to cellular signaling. Red-fleshed apple rich in ACNs suggested an anti-inflammatory effect while white-fleshed apple reduced the complement system protein-related. An apple matrix effect reduced inflammatory proteins regardless their ACN content.
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Project description:Fipronil is a widely-used broad-spectrum phenylpyrazole insecticide. It has been shown that fipronil increases the hepatic metabolism of thyroid hormone in the rat, which may induce compensatory mechanisms at the level of the thyroid gland itself. Here, we studied the effect of fipronil on the transcriptome of the thyroid gland in the rat. Adult (2- to 3-month-old) female Wistar rats were treated per os with fipronil (3 mg/kg) or the vehicle alone for 14 days. The transcriptome of their thyroid gland was analyzed using Agilent 4x44K microarrays. Thyroid gland gene expression was measured from female Wistar rats treated with vehicle (n = 10) or fipronil (n = 10) using a dye switch design.
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Project description:Acrylamide is a reproductive toxicant that has been detected in foods such as potato chips and breads. The consequences of chronic exposure to acrylamide in the human diet are unknown; however we previously reported that exposure to acrylamide at levels equivalent to human exposure produced high levels of genetic damage in early male germ cells of mice [Nixon et al. ToxSci 129(1), 135–145 (2012)]. In the present study, we examined changes in testicular gene expression in these mice to examine the potential mechanisms involved in acrylamide induced DNA damage in male germ cells and to provide a better understanding of the reproductive toxic effects of acrylamide in the male. Adult male mice were subjected to chronic acrylamide exposure via the drinking water at concentrations of 0, 0.001, 0.01, 0.1, 1 and 10 µg/ml for 1, 6 and 12 months. The testes were collected at each time point for RNA extraction and hybridization on an Illumina Sentrix Mouse ref-8 v2 Beadchip.
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2015-09-23 | E-GEOD-73307 | biostudies-arrayexpress
Project description:Male rats from one of four strains (Wistar, AA, HAD or P) were housed individually in standard hanging rodent cages (Ehret, Emmendingen, Germany) on a 12-hour light-dark cycle with lights on at 07:00 a.m.. Animals were provided with food (Sniff, Soest, Germany), tap water, 5, 10 and 20% (v/v) ethanol solutions ad libidum for 12 months. Control animals did not receive any alcohol. P rats and HAD rats were provided by Ting-Kai Li, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda. AA rats were provided by Petri Hyytiä and Kalervo Kiianmaa, Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland. To find out which genes are differentially expressed in response to alcohol consumption, we investigated the pancreas of the animals with respect to gene expression in alcohol-drinking and control animals. Animals with the highest alcohol consumption were chosen from a series of rats. We obtained microarray data from pancreatic tissue of these animals by using Affymetrix RG U34A microarrays, which contain probes for 8799 transcripts.
2009-12-31 | E-MEXP-776 | biostudies-arrayexpress
Project description:Thyroid nodules occur in about 60% of the population. Current diagnostic strategies, however, often fail at distinguishing malignant nodules before surgery, thus leading to unnecessary, invasive treatments. As proteins are involved in all physio/pathological processes, a proteome investigation of biopsied nodules may help correctly classify and identify malignant nodules and discover therapeutic targets. Quantitative mass spectrometry data-independent acquisition (DIA) enables highly reproducible and rapid throughput investigation of proteomes. An exhaustive spectral library of thyroid nodules is essential for DIA yet still unavailable. This study presents a comprehensive thyroid spectral library covering five types of thyroid tissue: multinodular goiter, follicular adenoma, follicular and papillary thyroid carcinoma, and normal thyroid tissue. Our library includes 925,330 transition groups, 157,548 peptide precursors, 121,960 peptides, 9941 protein groups, and 9826 proteins from proteotypic peptides. This library resource was evaluated using three papillary thyroid carcinoma samples and their corresponding adjacent normal thyroid tissue, leading to effective quantification of up to 7863 proteins from biopsy-level thyroid tissues.
2022-05-20 | PXD026395 | Pride
Project description:Transcriptional profiling of rat liver comparing male rats with congenital hypothyrodism (CH) vs intact at adulhood. Here we studied how CH influences liver gene expression program in adulthood. Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology but its specific influence in liver is less understood. Here we studied how CH influences liver gene expression program in adulthood. Pregnant rats were given anti-thyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as a reduction in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, feed efficiency increased in CH and this was accompanied by significant catch-up growth. On PND80, significant reduction in body mass, tail length, and circulating IGF-I remained in CH rats. On the other hand, mRNA levels of known GH targeted genes were significantly up-regulated. Serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in expression for hepatic genes involved in lipid metabolism with an increased transcription of PPAR and reduced expression of genes involved in fatty acids and cholesterol uptake, cellular sterol efflux, triglycerides assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to hypothyroidism onset in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters, and to T3 replacement with enhanced activation of lipogenic transcriptional program. In summary, we provided in vivo evidence that neonatal hypothyroidism causes long-lasting effects on hepatic transcriptional program and tissue sensitivity to hormone treatment. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood. Two conditions CH vs INTACT male rats. Biological replicates: Four independent hybridizations: 4 controls (age-matched intact rats) vs 4 CH (male rats with congenital hypothyroidism) on postnatal day 80 for a total of four arrays. One replicate per array.
2012-03-10 | E-GEOD-32705 | biostudies-arrayexpress
Project description:Acrylamide is known to produce follicular cell tumors of the thyroid in rats. RccHan Wistar rats were exposed in utero to a carcinogenic dose of acrylamide (3 mg/Kg bw/day) from gestation day 6 to delivery and then through their drinking water to postnatal day 35. In order to identify potential mechanisms of carcinogenesis in the thyroid glands, we used a transcriptomics approach. Thyroid glands were collected from male pups at 10 PM and female pups at 10 AM or 10 PM in order to establish whether active exposure to acrylamide influenced gene expression patterns or pathways that could be related to carcinogenesis. While all animals exposed to acrylamide showed changes in expected target pathways related to carcinogenesis, such as DNA repair, DNA replication, chromosome segregation, among others, animals that were sacrificed while actively drinking acrylamide-laced water during their active period at night showed increased changes in pathways related to oxidative stress, detoxification pathways, metabolism, and activation of checkpoint pathways, among others. In addition, thyroid hormones, T3 and T4, were increased in acrylamide-treated rats sampled at night, but not in quiescent animals, compared to controls. The data clearly indicate that time of day for sample collection is critical to identifying molecular pathways that are altered by the exposures. These results suggest that carcinogenesis in the thyroids of acrylamide treated rats may ensue from several different mechanisms such as hormonal changes and oxidative stress and not only from direct genotoxicity, as has been assumed to date.
2014-10-06 | GSE62026 | GEO
Project description:Background. Radioiodide 131I is commonly used to treat thyroid cancer and hyperthyroidism, and 131I releases during nuclear accidents have resulted in increased incidence of thyroid cancer in children. To develop a better understanding of underlying cellular mechanisms behind 131I exposure and identify potential biomarkers, the aim of this work was to study the long-term dose-related effects of 131I exposure in thyroid tissue and plasma in young rats. Materials and methods. Male Sprague Dawley rats (5-week-old) were i.v. injected with 0.5, 5.0, 50 or 500 kBq 131I (Dthyroid ca 1–1000 mGy), and killed after nine months at which time the thyroid and blood samples were collected. Gene expression microarray analysis (thyroid samples) and LC-MS/MS analysis (thyroid and plasma samples) were performed to assess differential gene and protein expression patterns in treated and corresponding untreated control samples. Bioinformatics analyses were performed using the DAVID functional annotation tool and Ingenuity Pathway Analysis (IPA). Results. Nine 131I exposure-related biomarkers (Afp and RT1-Bb,ARF3, DLD, IKBKB, NONO, RAB6A, RPN2, and SLC25A5) were identified in thyroid tissue. Four dose-related biomarker candidates (APRT, LDHA) and (TGM3 and DSG4) were identified in thyroid and plasma, respectively. Candidate biomarkers for thyroid function were the upstream regulator PPARG and the proteins ACADL and SORBS2 (all activities), TPO and TG (low activities)). 131I exposure was shown to have a profound effect on metabolism, the immune system, apoptosis and cell death. Furthermore, several signalling pathways essential for normal cellular function (actin cytoskeleton signalling, HGF signalling, NRF2-mediated oxidative stress, integrin signalling, calcium signalling) were also significantly regulated. Conclusion. Exposure-related and dose-related effects on gene and protein expression were observed, thereby identifying several candidate genes that could be used as potential biomarkers for exposure, absorbed dose and thyroid function.
2020-12-07 | PXD017715 | Pride