scholarly journals PSX-39 Late-Breaking Abstract: Characterization of epigenetic and transcriptional landscape in heat stressed rats using ATAC-seq and RNA-seq

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 353-354
Author(s):  
Jinhuan Dou ◽  
Flavio Schenkel ◽  
Ying Yu ◽  
Yachun Wang

Abstract Understanding animal physiology and identifying reliable biomarkers may help to establish effective management strategies for the prevention of heat stress (HS). However, little is known about the molecular mechanism of mammal tolerance to high temperatures. In a previous study with Sprague-Dawley rats, we performed RNA-seq assays on the liver of rats in control (CT; 22 ℃, n = 5) and heat stress (HS120; 42 ℃ for 120 min, n = 5) groups. A total of 3,909 differential expression genes (DEGs, Q < 0.05) were observed. This study was conducted to further examine the epigenetic landscape in the liver of rats under HS and identify transcription factors (TFs), as well as their regulated genes. Three liver tissues were selected from the RNA-seq samples and performed an Assay for Transpose Accessible Chromatin (ATAC-seq). Peaks meeting criteria of P< 0.05 and |Fold Change| >1.5 were considered as differential peaks. All ATAC-seq libraries generated an expected distribution of the insert fragment lengths, with the majority of fragments being small, which characterize inter-nucleosomal open chromatin, and progressively fewer fragments of larger size, which are spanning nucleosomes. The accessibility of transcriptional start sites (TSS) was significantly enriched. After merging data, 2,356 differential peaks showed CT having more accessible TSS than H120 and only 230 differential peaks showed H120 group having more accessible TSS than CT. Thirty-six and 22 TF motifs were predicted by up- and down-regulated differential peaks in H120 vs. CT. Together with the previous DEG results, we proposed candidate TFs annotated to Cebpa, Foxa4, and Sp3 DEGs, which are involved in the regulation of oxidative stress. In summary, we showed that nuclear chromatin in the liver of heat stressed rats was less open than that of control rats. We suggest that the TFs (Cebpa, Foxa4, and Sp3) may be involved in the physiological regulation of HS.

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinhuan Dou ◽  
Angela Cánovas ◽  
Luiz F. Brito ◽  
Ying Yu ◽  
Flavio S. Schenkel ◽  
...  

Understanding heat stress physiology and identifying reliable biomarkers are paramount for developing effective management and mitigation strategies. However, little is known about the molecular mechanisms underlying thermal tolerance in animals. In an experimental model of Sprague–Dawley rats subjected to temperatures of 22 ± 1°C (control group; CT) and 42°C for 30 min (H30), 60 min (H60), and 120 min (H120), RNA-sequencing (RNA-Seq) assays were performed for blood (CT and H120), liver (CT, H30, H60, and H120), and adrenal glands (CT, H30, H60, and H120). A total of 53, 1,310, and 1,501 differentially expressed genes (DEGs) were significantly identified in the blood (P < 0.05 and |fold change (FC)| >2), liver (P < 0.01, false discovery rate (FDR)–adjusted P = 0.05 and |FC| >2) and adrenal glands (P < 0.01, FDR-adjusted P = 0.05 and |FC| >2), respectively. Of these, four DEGs, namely Junb, P4ha1, Chordc1, and RT1-Bb, were shared among the three tissues in CT vs. H120 comparison. Functional enrichment analyses of the DEGs identified in the blood (CT vs. H120) revealed 12 biological processes (BPs) and 25 metabolic pathways significantly enriched (FDR = 0.05). In the liver, 133 BPs and three metabolic pathways were significantly detected by comparing CT vs. H30, H60, and H120. Furthermore, 237 BPs were significantly (FDR = 0.05) enriched in the adrenal glands, and no shared metabolic pathways were detected among the different heat-stressed groups of rats. Five and four expression patterns (P < 0.05) were uncovered by 73 and 91 shared DEGs in the liver and adrenal glands, respectively, over the different comparisons. Among these, 69 and 73 genes, respectively, were proposed as candidates for regulating heat stress response in rats. Finally, together with genome-wide association study (GWAS) results in cattle and phenome-wide association studies (PheWAS) analysis in humans, five genes (Slco1b2, Clu, Arntl, Fads1, and Npas2) were considered as being associated with heat stress response across mammal species. The datasets and findings of this study will contribute to a better understanding of heat stress response in mammals and to the development of effective approaches to mitigate heat stress response in livestock through breeding.


2019 ◽  
Vol 81 ◽  
pp. 12-19 ◽  
Author(s):  
Jinhuan Dou ◽  
Yuri R. Montanholi ◽  
Zezhao Wang ◽  
Zhongshu Li ◽  
Ying Yu ◽  
...  

Molecules ◽  
2015 ◽  
Vol 20 (11) ◽  
pp. 20240-20253 ◽  
Author(s):  
Kui-Jin Kim ◽  
Kye-Yoon Yoon ◽  
Hee-Do Hong ◽  
Boo-Yong Lee

2020 ◽  
Author(s):  
Keyang Wu ◽  
Yang Li ◽  
Peipei Pan ◽  
Zengqiang Li ◽  
Yige Yu ◽  
...  

Abstract Background: Vinclozolin is not only a common dicarboximide fungicide used to protect crops against diseases but also an endocrine disruptor. This study aimed to investigate the effects of gestational vinclozolin exposure on the development of rat fetal Leydig cells.Methods: Female pregnant Sprague-Dawley rats were exposed to vinclozolin (0, 25, 50, and 100 mg/kg body weight/day) by oral gavage from gestational day 14 to 21.Results: Vinclozolin dose-dependently depressed serum testosterone levels at doses of 50 and 100 mg/kg and anogenital distance at 100 mg/kg. RNA-seq, qPCR, and Western blot showed that vinclozolin down-regulated the expression of Nr5a1 , Sox9 , Lhcgr , Cyp11a1 , Hsd3b1 , Hsd17b3 , Amh , Pdgfa , and Dhh and their encoded proteins. Vinclozolin depressed NR2F2-positive stem Leydig cell number at a dose of 100 mg/kg and also enhanced autophagy in the testis.Conclusion: Vinclozolin disrupts fetal Leydig cell development via several pathways.


2021 ◽  
Author(s):  
Krzysztof Kotlarz ◽  
Magda Mielczarek ◽  
Yachun Wang ◽  
Jinhuan Dou ◽  
Tomasz Suchocki ◽  
...  

Abstract Since global temperature is expected to rise by 2℃ in 2050 heat stress may become the most severe environmental factor. In the study, we illustrate the application of mixed linear models for the analysis of whole transcriptome expression in livers and adrenal tissues of Sprague-Dawley rats obtained by a heat stress experiment. By applying those models, we considered four sources of variation in transcript expression, comprising transcripts (1), genes (2), Gene Ontology terms (3), and Reactome pathways (4) and focussed on accounting for the similarity within each source, which was expressed as a covariance matrix. Models based on transcripts or genes levels explained a larger proportion of log2 fold change than models fitting the functional components of Gene Ontology terms or Reactome pathways. In the liver, among the most significant genes were PNKD and TRIP12. In the adrenal tissue, one transcript of the SUCO gene was expressed more strongly in the control group than in the heat-stress group. PLEC had two transcripts, which were significantly overexpressed in the heat-stress group. PER3 was significant only on gene level. Moving to the functional scale, five Gene Ontologies and one Reactome pathway were significant in the liver. They can be grouped into ontologies related to DNA repair, histone ubiquitination, the regulation of embryonic development and cytoplasmic translation. Linear mixed models are valuable tools for the analysis of high-throughput biological data. Their main advantages are the possibility to incorporate information on covariance between observations and circumventing the problem of multiple testing.


2005 ◽  
Vol 288 (6) ◽  
pp. R1783-R1790 ◽  
Author(s):  
Douglas G. Whyte ◽  
Alan Kim Johnson

Blood flow is redistributed from the viscera to the periphery during periods of heat stress to maximize heat loss. The heat-induced redistribution of blood flow is strongly influenced by nonthermal inputs such as hydration status. At present, little is known about where thermal and nonthermal information is integrated to generate an appropriate effector response. Recently, the periventricular tissue that surrounds the anteroventral third ventricle (AV3V) has been implicated in the integration of thermal and osmotic information. The purpose of the present study was to determine the effects of electrolytic lesions of the AV3V on the cardiovascular response to a passive heat stress in unanesthetized, free-moving male Sprague-Dawley rats. Core temperature was elevated at a constant rate of ∼0.03°C/min in sham- and AV3V-lesion rats using an infrared heat lamp. Changes in mesenteric and hindquarter vascular resistance were determined using Doppler flow probes, and heat-induced salivation was estimated using the spit-print technique. The rise in mean arterial pressure (MAP), heart rate (HR), and mesenteric resistance in response to elevations in core temperature were all attenuated in AV3V-lesion rats; however, hindquarter resistance was unaffected. Heat-induced salivation was also diminished. In addition, AV3V-lesion rats were more affected by the novelty of the experimental environment, resulting in a higher basal core temperature, HR, and MAP. These results indicate that AV3V lesions disrupt the cardiovascular and salivatory response to a passive heat stress in rats and produce an exaggerated stress-induced fever triggered by a novel environment.


1996 ◽  
Vol 80 (1) ◽  
pp. 357-362 ◽  
Author(s):  
H. L. Fernandez ◽  
C. A. Hodges-Savola

This work addresses the physiological regulation of the tetrameric (G4) form of acetylcholinesterase (AChe) in end-plate regions of anterior gracilis muscles from adult male Sprague-Dawley rats subjected to short-term low-intensity treadmill exercise. Experiments involved analyses of muscle AChe molecular form activities, endogenous calcitonin gene-related peptide (CGRP) levels, and the effect of exogenous CGRP on AChe forms after exercise. Animals were exercised twice per day for 1 or 2 days. Daily training sessions of 135 min (10 min of walking alternating with 5 min of resting) were separated by a 105-min resting period. Results show that exercise causes a slight decline in endogenous CGRP and a selective increase in G4 AChe that is partially reversed by treatment with exogenous CGRP. These findings indicate that CGRP influences the mechanism(s) by which G4 AChe in intact fast-twitch anterior gracilis muscles adapts to enhanced motor activity. They are also consistent with the hypothesis that, in addition to acetylcholine, neurogenic CGRP participates in the regulation of G4 AChe at the neuromuscular junction.


1978 ◽  
Vol 79 (1) ◽  
pp. 133-134 ◽  
Author(s):  
M. B. TER HAAR ◽  
CATHERINE A. WILSON

*A.R.C. Institute of Animal Physiology, Babraham, Cambridge, CB2 4AT, and ‡Department of Physiology, Royal Veterinary College, London, NW1 OTU (Received 28 March 1978) Ovulation can be induced precociously in the prepubertal female rat by the administration of pregnant mare serum gonadotrophin (PMSG), provided that the animal weighs over 60 g (Wilson, Endersby & McDonald, 1974). The hormonal changes brought about by this treatment have been studied (J. C. Buckingham, M. B. ter Haar, A. S. McNeilly & C. A. Wilson, data to be published) and it has been found that the preovulatory concentrations of radioimmunoassayable luteinizing hormone (LH) varied according to the antiserum used. These findings are described in the present communication. Female Sprague–Dawley rats (Tuck & Sons, Rayleigh, Essex) were brought into the department on day 21 of life, kept under conditions of controlled lighting (lights on 05.00–19.00 h) and provided with pelleted rat diet (No. 86, Dixon &


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