Dataset Information

Flutamide-induced alterations in transcriptional profiling of neonatal porcine ovaries.

ABSTRACT: Background:Androgens are involved in the regulation of ovarian development during fetal/neonatal life. Environmental chemicals displaying anti-androgenic activities may affect multiple signal transduction pathways by blocking endogenous androgen action. The aim of the current study was to examine effects of the anti-androgen flutamide on the expression of coding transcripts and long non-coding RNAs (lncRNAs) in neonatal porcine ovaries. By employing RNA-Seq technology we aimed to extend our understanding of the role of androgens in neonatal folliculogenesis and examine the impact of the anti-androgen flutamide on ovarian function. Method:Piglets were subcutaneously injected with flutamide (50?mg/kg BW) or corn oil (controls) between postnatal days 1 and 10 (n?=?3/group). Ovaries were excised from the 11-day-old piglets and total cellular RNAs were isolated and sequenced. Results:Flutamide-treated piglet ovaries showed 280 differentially expressed genes (DEGs; P-adjusted?

SUBMITTER: Knapczyk-Stwora K

PROVIDER: S-EPMC6446412 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Flutamide-induced alterations in transcriptional profiling of neonatal porcine ovaries.

Knapczyk-Stwora Katarzyna K Nynca Anna A Ciereszko Renata E RE Paukszto Lukasz L Jastrzebski Jan P JP Czaja Elzbieta E Witek Patrycja P Koziorowski Marek M Slomczynska Maria M

Journal of animal science and biotechnology 20190403

<h4>Background</h4>Androgens are involved in the regulation of ovarian development during fetal/neonatal life. Environmental chemicals displaying anti-androgenic activities may affect multiple signal transduction pathways by blocking endogenous androgen action. The aim of the current study was to examine effects of the anti-androgen flutamide on the expression of coding transcripts and long non-coding RNAs (lncRNAs) in neonatal porcine ovaries. By employing RNA-Seq technology we aimed to extend ...[more]

PMID: 30988948

Similar Datasets

Project description:BackgroundAging is a major risk factor for the development of many diseases, and the liver, as the most important metabolic organ, is significantly affected by aging. It has been shown that the liver weight tends to increase in rodents and decrease in humans with age. Pigs have a genomic structure, with physiological as well as biochemical features that are similar to those of humans, and have therefore been used as a valuable model for studying human diseases. The molecular mechanisms of the liver aging of large mammals on a comprehensive transcriptional level remain poorly understood. The pig is an ideal model animal to clearly and fully understand the molecular mechanism underlying human liver aging.MethodsIn this study, four healthy female Yana pigs (an indigenous Chinese breed) were investigated: two young sows (180-days-old) and two old sows (8-years-old). High throughput RNA sequencing was performed to evaluate the expression profiles of messenger RNA, long non-coding RNAs, micro RNAs, and circular RNAs during the porcine liver aging process. Gene Ontology (GO) analysis was performed to investigate the biological functions of age-related genes.ResultsA number of age-related genes were identified in the porcine liver. GO annotation showed that up-regulated genes were mainly related to immune response, while the down-regulated genes were mainly related to metabolism. Moreover, several lncRNAs and their target genes were also found to be differentially expressed during liver aging. In addition, the multi-group cooperative control relationships and constructed circRNA-miRNA co-expression networks were assessed during liver aging.ConclusionsNumerous age-related genes were identified and circRNA-miRNA co-expression networks that are active during porcine liver aging were constructed. These findings contribute to the understanding of the transcriptional foundations of liver aging and also provide further references that clarify human liver aging at the molecular level.

Project description:Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, representing the most common form of liver cancer. As HCC incidence and mortality continue to increase, there is a growing need for improved translational animal models to bridge the gap between basic HCC research and clinical practice to improve early detection and treatment strategies for this deadly disease. Recently the Oncopig cancer model-a novel transgenic swine model that recapitulates human cancer through Cre recombinase induced expression of KRAS G12D and TP53 R167H driver mutations-has been validated as a large animal translational model for human HCC. Due to the similar size, anatomy, physiology, immunology, genetics, and epigenetics between pigs and humans, the Oncopig has the potential to improve translation of novel diagnostic and therapeutic modalities into clinical practice. Recent studies have demonstrated the importance of tumor cells in shaping its surrounding microenvironment into one that is more proliferative, invasive, and metastatic; however, little is known about the impact of microenvironment signaling on HCC tumor biology and differential gene expression between HCC tumors and its tumor microenvironment (TME). In this study, transcriptional profiling was performed on Oncopig HCC xenograft tumors (n = 3) produced via subcutaneous injection of Oncopig HCC cells into severe combined immunodeficiency (SCID) mice. To differentiate between gene expression in the tumor and surrounding tumor microenvironment, RNA-seq reads originating from porcine (HCC tumor) and murine (microenvironment) cells were bioinformatically separated using Xenome. Principle component analysis (PCA) demonstrated clustering by group based on the expression of orthologous genes. Genes contributing to each principal component were extracted and subjected to functional analysis to identify alterations in pathway signaling between HCC cells and the microenvironment. Altered expression of genes associated with hepatic fibrosis deposition, immune response, and neo angiogenesis were observed. The results of this study provide insights into the interplay between HCC and microenvironment signaling in vivo, improving our understanding of the interplay between HCC tumor cells, the surrounding tumor microenvironment, and the impact on HCC development and progression.

Project description:To determine the transcriptional profile of synovium during the molecular phase of post-traumatic osteoarthritis, anterior cruciate ligament transections (ACL) were performed in 36 Yucatan minipigs. Equal numbers were randomly assigned to no further treatment, ACL reconstruction or repair. Perimeniscal synovium for histopathology and RNA-sequencing was harvested at 1 and 4 weeks post-operatively and from six healthy control animals. Microscopic synovitis scores significantly worsened at 1 (p < 0.001) and 4 weeks (p = 0.003) post-surgery relative to controls, and were driven by intimal hyperplasia and increased stromal cellularity without inflammatory infiltrates. Synovitis scores were similar between no treatment, reconstruction, and repair groups (p ≥ 0.668). Relative to no treatment at 1 week, 88 and 367 genes were differentially expressed in the reconstruction and repair groups, respectively (227 and 277 at 4 weeks). Relative to controls and with the treatment groups pooled, 1,683 transcripts were concordantly differentially expressed throughout the post-surgery time-course. Affected pathways included, proteolysis_connective tissue degradation (including upregulations of protease-encoding MMP1, MMP13, and ADAMTS4), and development_cartilage development (including upregulations of ACAN, SOX9, and RUNX2), among others. Using linear regression, significant associations of post-surgery synovial expression levels of 20 genes with the articular cartilage glycosaminoglycan loss were identified. These genes were predominantly related to embryonic skeletal system development and included RUNX2. In conclusion, this study confirmed an increased synovial expression of genes that may serve as targets to prevent cartilage degradation, including MMP1, MMP13, and ADAMTS4, in knees with microscopic synovitis and cartilage proteoglycan loss. Attractive novel targets include regulators of embryonic developmental processes in synovium. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Dataset Information

Flutamide-induced alterations in transcriptional profiling of neonatal porcine ovaries.

Publications

Flutamide-induced alterations in transcriptional profiling of neonatal porcine ovaries.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets