165 Effect of Dimethyl Sulfoxide Supplementation During In Vitro Maturation on the Genetic Expression Pattern of Bovine Blastocyst

2018 ◽  
Vol 30 (1) ◽  
pp. 222
Author(s):  
A. E. Ynsaurralde-Rivolta ◽  
M. Suvá ◽  
R. Bevacqua ◽  
L. Rodriguez-Alvarez ◽  
A. Velasquez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Fragmentation ◽  
Expression Pattern ◽  
In Vitro Maturation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Stem Cell Differentiation ◽  
Marker Genes ◽  
Vitro Fertilization

Supplementation of bovine oocytes with 0.5% (v/v) dimethylsulfoxide (DMSO) during in vitro maturation (IVM) results in increased blastocysts rates (Ynsaurralde et al. 2016 Reprod. Fertil. Dev. 29, 201-202). Recently, an important role of DMSO in stem cell differentiation has been observed, attributed to modulation of gene expression. However, the effect of DMSO suplementation during in vitro maturation on gene expression profiles and embryo quality have not been evaluated so far. Thus, we examinated the effect of DMSO during IVM on the expression of some key genes (Sox2, Oct4, and Cdx2) and on the degree of DNA fragmentation at the blastocyst stage. To this aim, cumulus–oocyte complexes collected from slaughterhouse ovaries were matured in TCM-199 containing 10% fetal bovine serum, 10 µg mL−1 FSH, 0.3 mM sodium pyruvate, 100 mM cysteamine, and 2% antibiotic-antimycotic for 24 h, at 6.5% CO2 in humidified air and 38.5°C. Maturation media was supplemented with 0, 0.5, or 0.75% (v/v) DMSO. In vitro fertilization (IVF) was performed with 16 × 106 spermatozoa per mL for 5 h. Afterwards, presumptive zygotes were cultured in SOF for 7 days at 38.5°C and 5% O2. Three pools of 5 blastocysts were analysed for each treatment. Gene expression analysis was performed by real-time qPCR and DNA fragmentation of blastocysts was measured by TUNEL assay (n = 8, 7, and 14 blastocysts analysed for 0, 0.5, and 0.75% v/v DMSO, respectively). The results were statistically analysed using ANOVA with a completely randomised model by InfoStat software Version 1.1 (https://www.infostat.com.ar/). The pluripotency marker genes Sox2 and Oct4 were up-regulated in blastocysts only when the oocytes were matured in 0.75% DMSO, whereas the trophoblastic marker Cdx2 showed no differences among treatments. No differences were detected in the number of TUNEL-positive cells among treatments: 10/65 (15%) in 0%, 19/110 (18%) in 0.5%, and 18/98 (20%) in 0.75% (v/v) DMSO. In conclusion, supplementation with 0.5% (v/v) DMSO, as previously published, increases the production of blastocysts without disrupting the expression pattern of the evaluated genes.

163 EFFECTS OF DIFFERENT IN VITRO MATURATION SYSTEMS ON EMBRYO DEVELOPMENT IN BOVINE PREPUBERTAL AND ADULT DONORS

2014 ◽  
Vol 26 (1) ◽  
pp. 195
Author(s):  
S. M. Bernal ◽  
J. Heinzmann ◽  
D. Herrmann ◽  
U. Baulain ◽  
A. Lucas-Hahn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Embryo Development ◽  
In Vitro Maturation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Developmental Competence ◽  
In Vitro Production ◽  
Lactating Cows

Prepubertal bovine females have been suggested as a source of oocytes in order to accelerate genetic gain and decrease the generation interval. However, prepubertal oocytes have a lower developmental competence than their adult counterparts. In vitro maturation (IVM) systems using cyclic AMP (cAMP) regulators and 30-h culture have been suggested to improve blastocyst in vitro production rates from bovine oocytes (Albuz et al., 2010). The present study evaluated the effects of an addition of the cAMP modulators forskolin, 3-isobutyl-1-methylxanthine (IBMX), and cilostamide during extended IVM on blastocyst yields and gene expression in prepubertal and adult bovine females. Holstein-Friesian donors were submitted to ovum pick-up twice per week. Oocytes from groups of 12 animals, including lactating cows (>2 lactations) and prepubertal donors (6–10 months old) were used in the following treatment groups: TCM24 (24-h IVM, routine protocol/control), cAMP30 (2-h pre-IVM culture using forskolin-IBMX and 30-h IVM adding cilostamide), DMSO30 [2-h pre-IVM culture and 30-h IVM with dimethyl sulfoxide (DMSO)/vehicle control]. In vitro-matured oocytes were fertilized and presumptive zygotes were cultured in vitro to assess embryo development. In vivo blastocysts were produced from superovulated cows and used for gene expression analysis. Cleavage rates, blastocyst formation, and mRNA abundance of selected genes were evaluated. The Glimmix procedure from SAS/STAT (SAS Institute Inc., Cary, NC, USA) was performed to compare blastocyst and cleavage rates. One-way ANOVA was implemented to evaluate gene expression. A total of 793 oocytes from the different sources were submitted to the IVM treatments. Cleavage rates (prepubertal donors: 64.6 ± 4%, 59.1 ± 6.4%, 53 ± 4.4%, cows: 55.1 ± 4.3%, 59 ± 6.5%, 50.8 ± 4.4%, for TCM24, cAMP30, and DMSO30, respectively; P > 0.05) and blastocyst/zygotes rates (prepubertal donors: 27 ± 6%; 21.8 ± 3.5%; 17.6 ± 2.4%; cows: 28 ± 3.3%; 27.7 ± 2.9%; 22.7 ± 3.2% for TCM24, cAMP30, and DMSO30, respectively; P > 0.05) did not differ among in vitro treatments. The mRNA relative abundance of the EGR1 gene was down-regulated 6-fold in all in vitro-produced blastocysts compared with their in vivo counterparts (P < 0.05). Gene expression profiles for SLC2A8, DNMT3B, BCL-XL, and PRDX1 were similar in in vitro and in vivo blastocysts. These results show similar embryo production patterns in prepubertal and adult donors. Furthermore, DMSO did not show effects on embryo developmental rates when used during IVM. The gene expression levels of EGR1 confirm our recent findings in blastocysts obtained from oocytes from slaughterhouse ovaries (data not presented), showing its usefulness as an embryo quality marker. These preliminary results indicate that oocyte developmental capacity in prepubertal donors can be similar to that of the adult donors without addition of cAMP modulators.

scholarly journals Transcriptome analysis of gravitational effects on mouse skeletal muscles under microgravity and artificial 1 g onboard environment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Risa Okada ◽  
Shin-ichiro Fujita ◽  
Riku Suzuki ◽  
Takuto Hayashi ◽  
Hirona Tsubouchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Transcriptome Analysis ◽  
Fiber Type ◽  
Expression Profiles ◽  
Space Station ◽  
Gene Expression Profiles

AbstractSpaceflight causes a decrease in skeletal muscle mass and strength. We set two murine experimental groups in orbit for 35 days aboard the International Space Station, under artificial earth-gravity (artificial 1 g; AG) and microgravity (μg; MG), to investigate whether artificial 1 g exposure prevents muscle atrophy at the molecular level. Our main findings indicated that AG onboard environment prevented changes under microgravity in soleus muscle not only in muscle mass and fiber type composition but also in the alteration of gene expression profiles. In particular, transcriptome analysis suggested that AG condition could prevent the alterations of some atrophy-related genes. We further screened novel candidate genes to reveal the muscle atrophy mechanism from these gene expression profiles. We suggest the potential role of Cacng1 in the atrophy of myotubes using in vitro and in vivo gene transductions. This critical project may accelerate the elucidation of muscle atrophy mechanisms.

Simulated microgravity using the Random Positioning Machine inhibits differentiation and alters gene expression profiles of 2T3 preosteoblasts

2005 ◽  
Vol 288 (6) ◽  
pp. C1211-C1221 ◽  
Author(s):  
Steven J. Pardo ◽  
Mamta J. Patel ◽  
Michelle C. Sykes ◽  
Manu O. Platt ◽  
Nolan L. Boyd ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alkaline Phosphatase ◽  
Bone Loss ◽  
Simulated Microgravity ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Underlying Mechanism ◽  
Bone Biology ◽  
Random Positioning Machine

Exposure to microgravity causes bone loss in humans, and the underlying mechanism is thought to be at least partially due to a decrease in bone formation by osteoblasts. In the present study, we examined the hypothesis that microgravity changes osteoblast gene expression profiles, resulting in bone loss. For this study, we developed an in vitro system that simulates microgravity using the Random Positioning Machine (RPM) to study the effects of microgravity on 2T3 preosteoblast cells grown in gas-permeable culture disks. Exposure of 2T3 cells to simulated microgravity using the RPM for up to 9 days significantly inhibited alkaline phosphatase activity, recapitulating a bone loss response that occurs in real microgravity conditions without altering cell proliferation and shape. Next, we performed DNA microarray analysis to determine the gene expression profile of 2T3 cells exposed to 3 days of simulated microgravity. Among 10,000 genes examined using the microarray, 88 were downregulated and 52 were upregulated significantly more than twofold using simulated microgravity compared with the static 1-g condition. We then verified the microarray data for some of the genes relevant in bone biology using real-time PCR assays and immunoblotting. We confirmed that microgravity downregulated levels of alkaline phosphatase, runt-related transcription factor 2, osteomodulin, and parathyroid hormone receptor 1 mRNA; upregulated cathepsin K mRNA; and did not significantly affect bone morphogenic protein 4 and cystatin C protein levels. The identification of gravisensitive genes provides useful insight that may lead to further hypotheses regarding their roles in not only microgravity-induced bone loss but also the general patient population with similar pathological conditions, such as osteoporosis.

Gene Expression Regulation underlying Osteo-, Adipo-, and Chondro-Genic Lineage Commitment of Human Mesenchymal Stem Cells

2013 ◽  
pp. 76-94 ◽  
Author(s):  
Ana M. Sotoca ◽  
Michael Weber ◽  
Everardus J. J. van Zoelen
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Expression Regulation ◽  
Expression Profiles ◽  
Human Mesenchymal Stem Cells ◽  
Gene Expression Profiles ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Lineage Commitment

Human mesenchymal stem cells have a high potential in regenerative medicine. They can be isolated from a variety of adult tissues, including bone marrow, and can be differentiated into multiple cell types of the mesodermal lineage, including adipocytes, osteocytes, and chondrocytes. Stem cell differentiation is controlled by a process of interacting lineage-specific and multipotent genes. In this chapter, the authors use full genome microarrays to explore gene expression profiles in the process of Osteo-, Adipo-, and Chondro-Genic lineage commitment of human mesenchymal stem cells.

171 THE EFFECT OF TRICHOSTATIN A ON THE DEVELOPMENT AND THE GLOBAL GENE EXPRESSION PATTERNS IN MOUSE EMBRYOS DEVELOPING IN VITRO

2008 ◽  
Vol 20 (1) ◽  
pp. 165
Author(s):  
X. S. Cui ◽  
X. Y. Li ◽  
T. Kim ◽  
N.-H. Kim
Keyword(s):  
Gene Expression ◽  
Trichostatin A ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Mouse Embryos ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Cell Stage

Trichostatin A (TSA) is an inhibitor of histone deacetylase and is able to alter gene expression patterns by interfering with the removal of acetyl groups from histones. The aim of this study was to determine the effect of TSA treatment on the development and gene expression patterns of mouse zygotes developing in vitro. The addition of 100 nm TSA to the culture medium did not affect the cleavage of mouse embryos (TSA treatment, 148/150 (99%) v. control, 107/107 (100%)); however, embryos that were treated with TSA arrested at the 2-cell stage (145/148, 98%). We estimated the number of nuclei in control and TSA-treated embryos by propidium iodide staining, taking into account the presence of any cells with two or more nuclei. At 62–63 h post-hCG stimulation, control zygotes had developed to the 4-cell stage and exhibited one nucleus in each blastomere, indicative of normal development. In contrast, we observed tetraploid nuclei in at least one blastomere in 20.8% (11/53) of the embryos that had been treated with TSA. At 28–29 h post-hCG stimulation (metaphase of the 1-cell stage), there was no difference in the mitotic index (as determined by analyzing the microtubule configuration) in the TSA group compared to the control group. At the 2-cell stage, however, we did not observe mitotic spindles and metaphase chromatin in embryos in the TSA treatment group compared to the controls. Interestingly, when embryos were cultured in TSA-free medium from 35 h post-hCG stimulation (S- or early G2-phase of the 2-cell stage) onward, almost all of them (47/50) developed to the blastocyst stage. In contrast, when embryos were cultured in TSA-free medium from 42 h post-hCG stimulation (middle G2-phase of the 2-cell stage) onward, they did not develop to the 4-cell stage. We used Illumina microarray technology to analyze the gene expression profiles in control and TSA-treated late 2-cell-stage embryos. Applied Biosystems Expression System software was used to extract assay signals and assay signal-to-noise ratio values from the microarray images. Our data showed that 897 genes were significantly (P < 0.05; 2-sample t-test) up- or down-regulated by TSA treatment compared to controls. Analysis using the PANTHER classification system (https://panther.appliedbiosystems.com) revealed that the 575 genes that were differentially expressed in the TSA group compared to the control were classified as being associated with putative biological processes or molecular function. Overall, in terms of putative biological processes, more nucleoside, nucleotide, and nucleic acid metabolism, protein metabolism and modification, signal transduction, developmental process, and cell cycle genes were differentially expressed between the TSA and control groups. In terms of putative molecular function, more nucleic acid-binding transcription factor and transferase genes were differentially expressed between the groups. The results collectively suggest that inhibition of histone acetylation in mouse embryos affects gene expression profiles at the time of zygotic genome activation, and this subsequently affects further development.

168 miRNA LEVELS DURING BOVINE PREIMPLANTATION EMBRYONIC DEVELOPMENT

2008 ◽  
Vol 20 (1) ◽  
pp. 164
Author(s):  
D. K. Berg ◽  
S. E. Beaumont ◽  
P. L. Pfeffer
Keyword(s):  
Cellular Proliferation ◽  
Expression Profiles ◽  
Polar Body ◽  
Gene Expression Profiles ◽  
Donor Cell ◽  
Vitro Fertilization ◽  
Mrna Targets ◽  
Copy Numbers ◽  
First Polar Body

MicroRNAs (miRNAs) are a class of naturally occurring non-coding RNAs that play a role in gene regulation. They are highly conserved, single-stranded RNAs, 22 nucleotides in length, that are cleaved from larger inactive hairpin precursor transcripts, and use the RNA interference-related pathways to repress their mRNA targets. They play diverse regulatory roles in cellular proliferation, morphogenesis, apoptosis, and differentiation. Maternal miRNAs are crucial for early mammalian development (Murchison et al. 2007 Genes Dev. 21, 682–693; Tang et al. 2007 Genes Dev. 21, 655–648), while sperm-borne miRNAs do not contribute significantly to miRNAs in the zygote (Amanai et al. 2006 Biol. Reprod. 75, 877–884). Our objective was to identify miRNAs that are expressed during bovine in vitro oocyte maturation (MII) and blastocyst stages as well as during parthenogenic development. MII oocytes (n = 1680) were generated from abattoir-derived oocytes and matured in vitro for 24 h. Cumulus cells were removed and the first polar body was visually assessed before the oocytes were frozen in liquid N2. Parthenogenic blastocysts (n = 575) were produced using ionomycin/6DMAP activation, and IVF blastocysts (n = 1150) were produced using standard in vitro fertilization followed by in vitro culture in synthetic oviduct fluid (Thompson et al. 2000 J. Reprod. Fertil. 118, 47–55). Blastocysts (grades 1 and 2) were selected on Day 7 post-activation/insemination and frozen in liquid N2. RNA was isolated using the mirVana miRNA isolation kit (Ambion, Scoresby, Victoria, Australia). miRNAs were quantified using the TaqMan� MicroRNA Human Panel-Early Access Kit (Applied Biosystems, Scoresby, Victoria, Australia) following the manufacturer's protocol. Absolute copy numbers per embryo were estimated. Of the 157 miRNAs in the panel, 102, 136, and 118 were detected above background in oocytes, IVF, and parthenogenic blastocysts, respectively. Only 28 miRNAs were present at over 100 copies in MII oocytes, with maximum levels reaching 1300 copies. Levels were generally much higher at blastocyst stages, with 21 miRNAs present at more than 10 000 copies. miR-16 was one of the most abundant miRNAs in all samples tested. Copy numbers per blastomere cell were 5-fold higher in IVF blastocysts compared to parthegenotic blastocysts for miR-19a, 21, and 30b. The low copy numbers of mature miRNAs before embryonic genome activation may have implications for somatic cell nuclear transfer experiments in that exogenously added miRNAs from the donor cell could impact on the embryonic gene expression profiles.

229 EXPRESSION OF mRNA ENCODING GLYCOLYTIC ENZYMES IN BOVINE CUMULUS CELLS DURING IN VITRO MATURATION: EFFECTS OF TIME AND FSH

2010 ◽  
Vol 22 (1) ◽  
pp. 272
Author(s):  
E. S. Caixeta ◽  
P. Ripamonte ◽  
M. F. Machado ◽  
R. B. da Silva ◽  
C. Price ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
In Vitro Maturation ◽  
Housekeeping Gene ◽  
Cumulus Cells ◽  
Glycolytic Enzymes ◽  
Mrna Abundance ◽  
Relative Expression ◽  
Significant Difference

Mammalian oocytes require pyruvate as an energy source for growth and resumption of meiosis. Because oocytes are not competent to carry out glycolysis, cumulus cells (CC) are responsible for metabolizing glucose into pyruvate and providing it to the oocyte through gap junctions. The understanding of the energetic metabolism of CC in culture conditions might provide basis for the improvement of COC in vitro maturation. The aim of this study was to determine the temporal patterns of mRNA expression of glycolytic enzymes [phosphofructokinase (PFKP), aldolase (ALDOA), triosephosphate isomerase (TPI), enolase (ENO1), pyruvate kinase (PKM2), and lactate dehydrogenase (LDHA)] in bovine CC during COC in vitro maturation with or without FSH. Immature COC (grades 1 and 2) were obtained from 2- to 8-mm follicles from abattoir ovaries (predominantly Bos indicus). Cumulus cells were separated from COC and frozen before (immature group) or after COC culture for 4, 8, 12, 16, and 20 hours with (10 ng/mL) or without FSH. Total RNA was extracted using RNeasy® (Qiagen, Valencia, CA, USA), and 100 ng of RNA was reverse transcribed using oligo dT primers and Omniscript® (Qiagen). Relative expression of target genes was assessed by real-time PCR using bovine-specific primers and Power SYBR green master mix in an ABI Prism® 7300. To select the most stable housekeeping gene for expression normalization, cyclophilin-A (CYC-A), GAPDH, and histone H2AFZ amplification profiles were compared using the geNorm applet for Microsoft Excel (Vandesompele J et al. 2002 Genome Biol. 3, 1-11); the most stable housekeeping gene was CYC-A. Relative expression values were calculated using the AACt method with efficiency correction (Pfaffl MW 2001 Nucleic Acids Res. 29, 2002-2007). Effects of time in culture and of FSH treatment were tested by ANOVA, and groups were compared by Tukey-Kramer Honestly Significant Difference test. Nonparametric analysis was used when data were not normally distributed. Abundance of mRNA of all glycolytic enzymes decreased during in vitro maturation with or without FSH. Expression of PFKP, ALDOA, TPI1, ENO1, and LDHA genes was decreased to around half of the initial value (time 0) by 4 to 8 h of culture (P < 0.05) and did not increase thereafter. A similar expression pattern was observed for PKM2, although mRNA abundance was reduced later in comparison with other enzymes; levels were decreased by 16 (without FSH) to 20 h (with FSH) of culture. The presence of FSH did not alter the overall temporal pattern of gene expression but decreased mRNA abundance for PFKP, ALDOA, and TPI1 at 20, 16 and 16 h of culture, respectively. In conclusion, gene expression of glycolytic enzymes decreased with time during COC in vitro maturation in cattle, and FSH did not have a major influence on this expression pattern. This study was supported by CAPES and FAPESP.

Patients who failed to conceive following an in vitro fertilization cycle can be clustered into different failure causes using gene expression hierarchical analysis†

2020 ◽  
Vol 103 (3) ◽  
pp. 599-607
Author(s):  
Chloé S Fortin ◽  
Scot Hamilton ◽  
Martin Laforest ◽  
Marie-Claude Léveillé ◽  
Marc-André Sirard
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Clustering Analysis ◽  
Gene Expression Pattern ◽  
Hierarchical Analysis ◽  
Stimulation Protocol ◽  
Follicular Cells ◽  
Vitro Fertilization ◽  
Different Response

Abstract The patient’s response to an IVF stimulation protocol is highly variable and thus difficult to predict. When a cycle fails, there are often no apparent or obvious reasons to explain the failure. Having clues on what went wrong during stimulation could serve as a basis to improve and personalize the next protocol. This exploratory study aimed to investigate if it is possible to distinguish different failure causes or different follicular responses in a population of nonpregnant IVF patients. Using qRT-PCR, we analyzed a panel of genes indicative of different failure causes in patients who did not achieve pregnancy following an IVF cycle. For each patient, a pool of follicular cells from all aspirated follicles was used as a sample which gives a global picture of the patient’s ovary and not a specific picture of each follicle. We performed hierarchical clustering analysis to split the patients according to the gene expression pattern. Hierarchical analysis showed that the population of nonpregnant IVF patients could be divided into three clusters. Gene expression was significantly different, and each cluster displayed a particular gene expression pattern. Follicular cells from patients in clusters 1, 2 and 3 displayed respectively a pattern of gene expression related to large incompetent follicles with a higher apoptosis (over matured), to follicles not ready to ovulate (under mature) and to an excess of inflammation with no visible symptoms. This study reinforces the idea that women often have different response to the same protocol and would benefit from more personalized treatments.

Gene Expression Profiles in Rat Liver Slices Exposed to Hepatocarcinogenic Enzyme Inducers, Peroxisome Proliferators, and 17α-Ethinylestradiol

2006 ◽  
Vol 25 (5) ◽  
pp. 379-395 ◽  
Author(s):  
Gisela Werle-Schneider ◽  
Andreas Wölfelschneider ◽  
Marie Charlotte von Brevern ◽  
Julia Scheel ◽  
Thorsten Storck ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rat Liver ◽  
Mode Of Action ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Peroxisome Proliferators ◽  
Liver Slices ◽  
Enzyme Inducers

Transcription profiling is used as an in vivo method for predicting the mode-of-action class of nongenotoxic carcinogens. To set up a reliable in vitro short-term test system DNA microarray technology was combined with rat liver slices. Seven compounds known to act as tumor promoters were selected, which included the enzyme inducers phenobarbital, α-hexachlorocyclohexane, and cyproterone acetate; the peroxisome proliferators WY-14,643, dehydroepiandrosterone, and ciprofibrate; and the hormone 17 α-ethinylestradiol. Rat liver slices were exposed to various concentrations of the compounds for 24 h. Toxicology-focused TOXaminer™ DNA microarrays containing approximately 1500 genes were used for generating gene expression profiles for each of the test compound. Hierarchical cluster analysis revealed that (i) gene expression profiles generated in rat liver slices in vitro were specific allowing classification of compounds with similar mode of action and (ii) expression profiles of rat liver slices exposed in vitro correlate with those induced after in vivo treatment (reported previously). Enzyme inducers and peroxisome proliferators formed two separate clusters, confirming that they act through different mechanisms. Expression profiles of the hormone 17 α-ethinylestradiol were not similar to any of the other compounds. In conclusion, gene expression profiles induced by compounds that act via similar mechanisms showed common effects on transcription upon treatment in vivo and in rat liver slices in vitro.

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