Identification of temporal patterns of gene expression in the uteri of immature, ovariectomized mice following exposure to ethynylestradiol

2003 ◽  
Vol 15 (2) ◽  
pp. 127-141 ◽  
Author(s):  
K. C. Fertuck ◽  
J. E. Eckel ◽  
C. Gennings ◽  
T. R. Zacharewski

Estrogen induction of uterine wet weight provides an excellent model to investigate relationships between changes in global gene expression and well-characterized physiological responses. In this study, time course microarray GeneChip data were analyzed using a novel approach to identify temporal changes in uterine gene expression following treatment of immature ovariectomized C57BL/6 mice with 0.1 mg/kg 17α-ethynylestradiol. Functional gene annotation information from public databases facilitated the association of changes in gene expression with physiological outcomes, which allowed detailed mechanistic inferences to be drawn regarding cell cycle control and proliferation, transcription and translation, structural tissue remodeling, and immunologic responses. These systematic approaches confirm previously established responses, identify novel estrogen-regulated transcriptional effects, and disclose the coordinated activation of multiple modes of action that support the uterotrophic response elicited by estrogen. In particular, it was possible to elucidate the physiological significance of the dramatic induction of arginase, a classic estrogenic response, by elucidating its mechanistic relevance and delineating the role of arginine and ornithine utilization in the estrogen-stimulated induction of uterine wet weight.

2009 ◽  
Vol 200 (2) ◽  
pp. 307-313 ◽  
Author(s):  
Jeniel E. Nett ◽  
Alexander J. Lepak ◽  
Karen Marchillo ◽  
David R. Andes

2010 ◽  
Vol 45 (3) ◽  
pp. 161-173 ◽  
Author(s):  
Cora J Fong ◽  
Lyle D Burgoon ◽  
Kurt J Williams ◽  
A Daniel Jones ◽  
Agnes L Forgacs ◽  
...  

Tamoxifen (TAM), the primary treatment for estrogen receptor (ER)-positive breast cancer, has been associated with an increased incidence of endometrial cancer in postmenopausal, but not premenopausal women. TAM elicits a partial ER-mediated uterotrophic response in immature rodents when compared with ethynylestradiol (EE), a potent ER agonist. However, cotreatment with 1000 μg/kg TAM antagonizes the uterotrophic effect induced by 30 μg/kg EE. To further investigate the anti-uterotrophic activity of TAM, immature, ovariectomized C57BL/6 mice were treated with a single oral dose of EE, TAM, EE+TAM, or vehicle, and harvested at 2, 4, 8, 12, 18, and 24 h or after three daily treatments at 72 h. Significant increases in uterine wet weight (UWW) were observed at 18 h for EE, TAM, and the mixture. However, mixture induction of UWW was significantly lower when compared with EE-induced uterotrophy at 72 h. This inhibitory effect is also reflected in decreases in luminal circumference, yet EE-induced luminal epithelial cell height was unaffected by cotreatment with TAM. Gene expression analysis using a 2×2 factorial cDNA microarray study design identified 2518 differentially expressed genes following EE treatment alone. However, only 290 EE-elicited gene expression changes were affected by TAM cotreatment, in a manner consistent with the anti-estrogenic response. These data suggest that TAM antagonism of EE-induced UWW increase involves the selective inhibition of EE-induced genes.


2019 ◽  
Vol 20 (18) ◽  
pp. 4585 ◽  
Author(s):  
Nikolai Genov ◽  
Stefano Castellana ◽  
Felix Scholkmann ◽  
Daniele Capocefalo ◽  
Mauro Truglio ◽  
...  

Cellular, organ, and whole animal physiology show temporal variation predominantly featuring 24-h (circadian) periodicity. Time-course mRNA gene expression profiling in mouse liver showed two subsets of genes oscillating at the second (12-h) and third (8-h) harmonic of the prime (24-h) frequency. The aim of our study was to identify specific genomic, proteomic, and functional properties of ultradian and circadian subsets. We found hallmarks of the three oscillating gene subsets, including different (i) functional annotation, (ii) proteomic and electrochemical features, and (iii) transcription factor binding motifs in upstream regions of 8-h and 12-h oscillating genes that seemingly allow the link of the ultradian gene sets to a known circadian network. Our multifaceted bioinformatics analysis of circadian and ultradian genes suggests that the different rhythmicity of gene expression impacts physiological outcomes and may be related to transcriptional, translational and post-translational dynamics, as well as to phylogenetic and evolutionary components.


2004 ◽  
Vol 84 (3) ◽  
pp. 367-376 ◽  
Author(s):  
C. Hansen ◽  
A. Fu ◽  
C. Li ◽  
W. T. Dixon ◽  
R. Christopherson ◽  
...  

Adipogenesis is of significant relevance from an agricultural perspective. Traits such as subcutaneous fat thickness, marbling and waste fat are of substantial economic importance in animal production. In order to discover more about the genetic basis of this process, a study was undertaken to examine the changes that occur daily in global gene expression as 3T3-L1 cells differentiate from preadipocyte to adipocyte. Duplicate RNA samples were collected daily during the differentiation process and probed with the Affymetrix U74Av2 GeneChip® microarray to allow the time-course analysis of the gene expression profile in these differentiating cells. Self-organizing maps (SOM) clustering was performed to extract patterns of expression over the course of the experiment (day 0 to day 6). The clustering generated nine distinct expression patterns containing between 74 and 420 genes/ESTs. Functional clusters and important chronological changes in the expression of key genes and gene groups were identified. The pattern of expression observed for many genes not only confirmed what has been shown previously for the early stages of differentiation, but also expanded this pattern to cover the whole differentiation process thus giving a very comprehensive overview of patterns and changes in gene expression over the time course of adipocyte differentiation. Key words: Adipocyte differentiation, gene expression, SOM clustering


2004 ◽  
Vol 78 (20) ◽  
pp. 11051-11060 ◽  
Author(s):  
Wei Xiang ◽  
Otto Windl ◽  
Gerda Wünsch ◽  
Martin Dugas ◽  
Alexander Kohlmann ◽  
...  

ABSTRACT The pathogenesis of prion diseases, a class of transmissible fatal neurodegenerative diseases in humans and animals, is still unclear. The aim of this study was to identify the differentially regulated genes that correlate with the development of prion diseases for a better understanding of their pathological mechanisms. We employed Affymetrix Mouse Expression Arrays 430A containing >22,000 transcripts and compared the global gene expression profiles from brains of mice who were intracerebrally inoculated with scrapie strains ME7 and RML with those from brains of uninfected and mock-infected mice. The microarray data were analyzed by Significance Analysis of Microarrays, revealing 121 genes whose expression increased at least twofold in both ME7- and RML-infected mouse brains, with an estimated false discovery rate of ≤5%. These genes encode proteins involved in proteolysis, protease inhibition, cell growth and maintenance, the immune response, signal transduction, cell adhesion, and molecular metabolism. The time course of expression generally showed up-regulation of these genes from 120 days postinoculation (dpi) for ME7-inoculated mouse brains and from 90 dpi for RML-inoculated mouse brains. The onset of elevated expression correlated temporally with the onset of PrPSc accumulation and the activation of glia, which may have contributed to neuronal cell death. Among the differentially regulated genes reported in the present study, the emergence of genes for several cathepsins and S100 calcium binding proteins was conspicuous. These and other genes reported here may represent novel potential diagnostic and therapeutic targets for prion disease.


Genomics ◽  
2021 ◽  
Vol 113 (1) ◽  
pp. 120-134
Author(s):  
Gaurav Sharma ◽  
Andrew I. Yao ◽  
Gregory T. Smaldone ◽  
Jennifer Liang ◽  
Matt Long ◽  
...  

2002 ◽  
Vol 9 (3) ◽  
pp. 145-155 ◽  
Author(s):  
Chang-Fu Peng ◽  
Yi Wei ◽  
Jeffrey M. Levsky ◽  
Thomas V. McDonald ◽  
Geoffrey Childs ◽  
...  

Significant progress has been made in defining pathways that mediate the formation of the mammalian heart. Little is known, however, about the genetic program that directs the differentiation of cardiac myocytes from their precursor cells. A major hindrance to this kind of investigation has been the absence of an appropriate cell culture model of cardiac myocyte differentiation. Recently, a subline of P19 cells (P19CL6) was derived that, following dimethyl sulfoxide (DMSO) treatment, differentiate efficiently over 10 days into spontaneously beating cardiac myocytes. We demonstrate that these cells are indeed cardiac myocytes as they express cell type-specific markers and exhibit electrophysiological properties indicative of cardiac myocytes. The requirement for DMSO stimulation in this paradigm was shown to be limited to the first 4 days, suggesting that critical events in the differentiation process occur over this interval. To uncover relationships among known genes and identify novel genes that mediate cardiac myocyte differentiation, a detailed time course of changes in global gene expression was carried out using cDNA microarrays. In addition to the activation of genes encoding cardiac transcription factors and structural proteins, increases were noted in the expression of multiple known genes and expressed sequence tags (ESTs). Analysis of the former suggested the involvement of a variety of signaling pathways in cardiac myocyte differentiation. The 16 ESTs whose expression was increased during the early, stimulus-dependent phase of cardiac myocyte differentiation may be novel regulators of this process. Thus this first report of large-scale changes in gene expression during cardiac myocyte differentiation has delineated relationships among the expression patterns of known genes and identified a number of novel genes that merit further study.


2008 ◽  
Vol 8 (2) ◽  
pp. 170-180 ◽  
Author(s):  
Silvia M. Salem-Izacc ◽  
Tie Koide ◽  
Ricardo Z. N. Vêncio ◽  
Suely L. Gomes

ABSTRACT Blastocladiella emersonii is an aquatic fungus of the Chytridiomycete class. During germination, the zoospore, a motile nongrowing cell, goes through a cascade of morphological changes that culminates with its differentiation into the germling cell, capable of coenocytic vegetative growth. Transcriptome analyses of B. emersonii cells were carried out during germination induced under various environmental conditions. Microarray data analyzing 3,563 distinct B. emersonii genes revealed that 26% of them are differentially expressed during germination in nutrient medium at at least one of the time points investigated. Over 500 genes are upregulated during the time course of germination under those conditions, most being related to cell growth, including genes involved in protein biosynthesis, DNA transcription, energetic metabolism, carbohydrate and oligopeptide transport, and cell cycle control. On the other hand, several transcripts stored in the zoospores are downregulated during germination in nutrient medium, such as genes involved in signal transduction, amino acid transport, and chromosome organization. In addition, germination induced in the presence of nutrients was compared with that triggered either by adenine or potassium ions in inorganic salt solution. Several genes involved in cell growth, induced during germination in nutrient medium, do not show increased expression when B. emersonii zoospores germinate in inorganic solution, suggesting that nutrients exert a positive effect on gene transcription. The transcriptome data also revealed that most genes involved in cell signaling show the same expression pattern irrespective of the initial germination stimulus.


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