scholarly journals Gene expression profiling ofcorpus luteumreveals the importance of immune system during early pregnancy in domestic sheep

2019 ◽  
Author(s):  
Kisun Pokharel ◽  
Jaana Peippo ◽  
Melak Weldenegodguad ◽  
Mervi Honkatukia ◽  
Meng-Hua Li ◽  
...  

AbstractThe majority of pregnancy loss in ruminants occurs during the preimplantation stage, which is thus the most critical period determining reproductive success. While ovulation rate is the major determinant of litter size in sheep, interactions among the conceptus,corpus luteumand endometrium are essential for pregnancy success. Here, we performed a comparative transcriptome study by sequencing total mRNA from corpus luteum (CL) collected during the preimplantation stage of pregnancy in Finnsheep, Texel and F1 crosses, and mapping the RNA-Seq reads to the latest Rambouillet reference genome. A total of 21,287 genes were expressed in our dataset. Highly expressed autosomal genes in the CL were associated with biological processes such as progesterone formation (STAR, CYP11A1, andHSD3B1) and embryo implantation (eg.TIMP1, TIMP2andTCTP). Among the list of differentially expressed genes, a group of sialic acid-binding immunoglobulin (Ig)-like lectins (Siglecs), solute carriers (SLC13A5, SLC15A2, SLC44A5) and chemokines (CCL5, CXCL13, CXCL9) were upregulated in Finnsheep, while four multidrug resistance-associated proteins (MRPs) were upregulated in Texel ewes. A total of 17 genes and two non-coding RNAs (ncRNA) were differentially expressed in breed-wise comparisons owing to flushing diet effect. Moreover, we report, for the first time in any species, several genes that are active in the CL during early pregnancy (includingSIGLEC13, SIGLEC14, SIGLEC6, MRP4, andCA5A). Importantly, functional analysis of differentially expressed genes suggested that Finnsheep have a better immune system than Texel and that high prolificacy in Finnsheep might be governed by immune system regulation.


Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 415 ◽  
Author(s):  
Kisun Pokharel ◽  
Jaana Peippo ◽  
Melak Weldenegodguad ◽  
Mervi Honkatukia ◽  
Meng-Hua Li ◽  
...  

The majority of pregnancy loss in ruminants occurs during the preimplantation stage, which is thus the most critical period determining reproductive success. Here, we performed a comparative transcriptome study by sequencing total mRNA from corpus luteum (CL) collected during the preimplantation stage of pregnancy in Finnsheep, Texel and F1 crosses. A total of 21,287 genes were expressed in our data. Highly expressed autosomal genes in the CL were associated with biological processes such as progesterone formation (STAR, CYP11A1, and HSD3B1) and embryo implantation (e.g., TIMP1, TIMP2 and TCTP). Among the list of differentially expressed genes, sialic acid-binding immunoglobulin (Ig)-like lectins (SIGLEC3, SIGLEC14, SIGLEC8), ribosomal proteins (RPL17, RPL34, RPS3A, MRPS33) and chemokines (CCL5, CCL24, CXCL13, CXCL9) were upregulated in Finnsheep, while four multidrug resistance-associated proteins (MRPs) were upregulated in Texel ewes. A total of 17 known genes and two uncharacterized non-coding RNAs (ncRNAs) were differentially expressed in breed-wise comparisons owing to the flushing diet effect. The significantly upregulated TXNL1 gene indicated potential for embryonic diapause in Finnsheep and F1. Moreover, we report, for the first time in any species, several genes that are active in the CL during early pregnancy (including TXNL1, SIGLEC14, SIGLEC8, MRP4, and CA5A).



2018 ◽  
Vol 50 (2) ◽  
pp. 668-678 ◽  
Author(s):  
Wen-Qian Zhang ◽  
Miao Zhao ◽  
Ming-Yu Huang ◽  
Ji-Long Liu

Background/Aims: Embryo implantation is an essential process for eutherian pregnancy, but this process varies across eutherians. The genomic mechanisms that led to the emergence and diversification of embryo implantation are largely unknown. Methods: In this study, we analyzed transcriptomic changes during embryo implantation in mice and rats by using RNA-seq. Bioinformatics and evolutionary analyses were performed to characterize implantation-associated genes in these two species. Results: We identified a total of 518 differentially expressed genes in mouse uterus during implantation, of which 253 genes were up-regulated and 265 genes were down-regulated at the implantation sites compared with the inter-implantation sites. In rat uterus, there were 374 differentially expressed genes, of which 284 genes were up-regulated and 90 genes were down-regulated. A cross-species comparison revealed that 92 up-regulated genes and 20 down-regulated genes were shared. The differences and similarities between mice and rats were investigated further at the gene ontology, pathway, network, and causal transcription factor levels. Additionally, we found that embryo implantation might have evolved through the recruitment of ancient genes into uterine expression. The evolutionary rates of the differentially expressed genes in mouse and rat uterus were significantly lower than those of the non-changed genes, indicating that implantation-related genes are evolutionary conserved due to high selection pressure. Conclusion: Our study provides insights into the molecular mechanisms involved in the evolution of embryo implantation.



2020 ◽  
Author(s):  
Nan Zhou ◽  
Jinku Bao ◽  
Yuping Ning

Abstract The ongoing COVID-19 pandemic in the world is caused by SARS-CoV-2, a new coronavirus firstly discovered in the end of 2019. It has led to more than 10 million confirmed cases and more than 500,000 confirmed deaths across 216 countries by 1 July 2020, according to WHO statistics. SARS-CoV-2, SARS-CoV, and MERS-CoV are alike, killing people, impairing economy, and inflicting long-term impacts on the society. However, no specific drug or vaccine has been approved as a cure for these viruses. The efforts to develop antiviral measures are hampered by insufficient understanding of molecular responses of human to viral infections. In this study, we collected experimentally validated human proteins that interact with SARS-CoV-2 proteins, human proteins whose expression, translation and phosphorylation levels experience significantly changes after SARS-CoV-2 or SARS-CoV infection, human proteins that correlate with COVID-19 severity, and human genes whose expression levels significantly changed upon SARS-CoV-2 or MERS-CoV infection. A database, H2V, was then developed for easy access to these data. Currently H2V includes: 332 human-SARS-CoV-2 protein-protein interactions; 65 differentially expressed proteins, 232 differentially translated proteins, 1298 differentially phosphorylated proteins, 204 severity associated proteins, and 4012 differentially expressed genes responding to SARS-CoV-2 infection; 66 differentially expressed proteins responding to SARS-CoV infection; and 6981 differentially expressed genes responding to MERS-CoV infection. H2V can help to understand the cellular responses associated with SARS-CoV-2, SARS-CoV and MERS-CoV infection. It is expected to speed up the development of antiviral agents and shed light on the preparation for potential coronavirus emergency in the future.Database url: http://www.zhounan.org/h2v



2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Mohadeseh Zarei Ghobadi ◽  
Sayed-Hamidreza Mozhgani ◽  
Mahdieh Farzanehpour ◽  
Farida Behzadian

Abstract Background Despite the high yearly prevalence of Influenza, the pathogenesis mechanism and involved genes have not been fully known. Finding the patterns and mapping the complex interactions between different genes help us to find the possible biomarkers and treatment targets. Methods Herein, weighted gene co-expression network analysis (WGCNA) was employed to construct a co-expression network among genes identified by microarray analysis of the pediatric influenza-infected samples. Results Three of the 38 modules were found as the most related modules to influenza infection. At a functional level, we found that the genes in these modules regulate the immune responses, protein targeting, and defense to virus. Moreover, the analysis of differentially expressed genes disclosed 719 DEGs between the normal and infected subjects. The comprehensive investigation of genes in the module involved in immune system and viral defense (yellow module) revealed that SP110, HERC5, SAMD9L, RTP4, C19orf66, HELZ2, EPSTI1, and PHF11 which were also identified as DEGs (except C19orf66) have the potential to be as the biomarkers and also drug targeting for the treatment of pediatric influenza. Conclusions The WGCN analysis revealed co-expressed genes which were involved in the innate immune system and defense to virus. The differentially expressed genes in the identified modules can be considered for designing drug targets. Moreover, modules can help to find pathogenesis routes in the future.



Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1521-1529 ◽  
Author(s):  
Randy L. Bogan ◽  
Melinda J. Murphy ◽  
Jon D. Hennebold

Luteolysis of the corpus luteum (CL) during nonfertile cycles involves a cessation of progesterone (P4) synthesis (functional regression) and subsequent structural remodeling. The molecular processes responsible for initiation of luteal regression in the primate CL are poorly defined. Therefore, a genomic approach was used to systematically identify differentially expressed genes in the rhesus macaque CL during spontaneous luteolysis. CL were collected before [d 10–11 after LH surge, mid-late (ML) stage] or during (d 14–16, late stage) functional regression. Based on P4 levels, late-stage CL were subdivided into functional-late (serum P4 > 1.5 ng/ml) and functionally regressed late (FRL) (serum P4 < 0.5 ng/ml) groups (n = 4 CL per group). Total RNA was isolated, labeled, and hybridized to Affymetrix genome microarrays that contain elements representing the entire rhesus macaque transcriptome. With the ML stage serving as the baseline, there were 681 differentially expressed transcripts (>2-fold change; P < 0.05) that could be categorized into three primary patterns of expression: 1) increasing from ML through FRL; 2) decreasing from ML through FRL; and 3) increasing ML to functional late, followed by a decrease in FRL. Ontology analysis revealed potential mechanisms and pathways associated with functional and/or structural regression of the macaque CL. Quantitative real-time PCR was used to validate microarray expression patterns of 13 genes with the results being consistent between the two methodologies. Protein levels were found to parallel mRNA profiles in four of five differentially expressed genes analyzed by Western blot. Thus, this database will facilitate the identification of mechanisms involved in primate luteal regression. Genes differentially expressed during spontaneous functional regression in the rhesus macaque corpus luteum are identified, which in turn will further our understanding of primate luteolysis.



2018 ◽  
Vol 46 (5) ◽  
pp. 1868-1878 ◽  
Author(s):  
Ming-Yu Huang ◽  
Wen-Qian Zhang ◽  
Miao Zhao ◽  
Can Zhu ◽  
Jia-Peng He ◽  
...  

Background/Aims: The mouse is widely used as an animal model for studying human embryo implantation. However, the mouse is unique in that both ovarian progesterone and estrogen are critical to implantation, whereas in the majority of species (e.g. human and hamster) implantation can occur in the presence of progesterone alone. Methods: In this study, we analyzed embryo-induced transcriptomic changes in the hamster uterus during embryo implantation by using RNA-seq. Differentially expressed genes were characterized by bioinformatic analysis. Results: We identified a total of 781 differentially expressed genes, of which 367 genes were up-regulated and 414 genes were down-regulated at the implantation site compared to the inter-implantation site. Functional clustering and gene network analysis highlighted the cell cycle process in uterus upon embryo implantation. By examining of the promoter regions of differentially expressed genes, we identified 7 causal transcription factors. Additionally, through connectivity map (CMap) analysis, multiple compounds were identified to have potential anti-implantation effects due to their ability to reverse embryo-induced transcriptomic changes. Conclusion: Our study provides a valuable resource for in-depth understanding of the mechanism underlying embryo implantation.



2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Arun Sudhagar ◽  
Reinhard Ertl ◽  
Gokhlesh Kumar ◽  
Mansour El-Matbouli

Abstract Background Tetracapsuloides bryosalmonae is a myxozoan parasite which causes economically important and emerging proliferative kidney disease (PKD) in salmonids. Brown trout, Salmo trutta is a native fish species of Europe, which acts as asymptomatic carriers for T. bryosalmonae. There is only limited information on the molecular mechanism involved in the kidney of brown trout during T. bryosalmonae development. We employed RNA sequencing (RNA-seq) to investigate the global transcriptome changes in the posterior kidney of brown trout during T. bryosalmonae development. Methods Brown trout were exposed to the spores of T. bryosalmonae and posterior kidneys were collected from both exposed and unexposed control fish. cDNA libraries were prepared from the posterior kidney and sequenced. Bioinformatics analysis was performed using standard pipeline of quality control, reference mapping, differential expression analysis, gene ontology, and pathway analysis. Quantitative real time PCR was performed to validate the transcriptional regulation of differentially expressed genes, and their correlation with RNA-seq data was statistically analyzed. Results Transcriptome analysis identified 1169 differentially expressed genes in the posterior kidney of brown trout, out of which 864 genes (74%) were upregulated and 305 genes (26%) were downregulated. The upregulated genes were associated with the regulation of immune system process, vesicle-mediated transport, leucocyte activation, and transport, whereas the downregulated genes were associated with endopeptidase regulatory activity, phosphatidylcholine biosynthetic process, connective tissue development, and collagen catabolic process. Conclusion To our knowledge, this is the first RNA-seq based transcriptome study performed in the posterior kidney of brown trout during active T. bryosalmonae development. Most of the upregulated genes were associated with the immune system process, whereas the downregulated genes were associated with other metabolic functions. The findings of this study provide insights on the immune responses mounted by the brown trout on the developing parasite, and the host molecular machineries modulated by the parasite for its successful multiplication and release.



2020 ◽  
Vol 60 (10) ◽  
pp. 1326
Author(s):  
Zhen Wang ◽  
Datao Wang ◽  
Tao Qin ◽  
Hengxing Ba ◽  
Guanning Wei ◽  
...  

Context Immune system has been claimed as the ‘main switch’ of tissue or organ regeneration. Among immune cells, macrophages stand out as important modulators in mutiple regeneration models, such as planarian, axolotl, mammalian hair and liver. As a unique model for mammals, deer antler is considered to ideal for studying complete mammalian organ regeneration. Studies have found that antler regeneration is a stem cell-based process and antler stem cells locate in the pedicle periosteum (PP). Although the regulatory roles of the immune system in other regeneration models have been extensively studied, they remain unstudied in antler regeneration. Aims To explore the possible role of macrophages in the PP cells (PPCs). Methods We treated PPCs with a macrophage-conditioned medium (MCM) and detected effects of MCM on proliferation, migration and apoptosis of the PPCs, and identified differentially expressed genes by using the RNA-seq technique. Key results We found that MCM enhanced proliferation rate and migration rate significantly and stimulated apoptosis of the PPCs. Using the RNA-seq technique, we identified 112 differentially expressed genes in the PPCs (38 downregulated and 74 upregulated) after the MCM treatment. Furthermore, gene-ontology annotation analyses showed that the upregulated genes were mainly involved in cell adhesion, chemotaxis, wound healing, growth factor-stimulated responses, and bone formation, and the downregulated genes were involved in regulation of biosynthesis. Conclusions MCM had a great influence on the antler stem cells, and macrophages might regulate antler regeneration through altering the microenvironment and gene-expression profiles of the PPCs. Implications We believe that the results of the present study would facilitate the discovery of the roles of immune system in antler stem cells and, thus, mammalian organ regeneration in general.



Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Gina Sykes ◽  
Yusra Batool ◽  
Joseph Kamtchum Tatuene ◽  
Sarah Zehnder ◽  
Glen C Jickling

Introduction: Immune system dysregulation occurs with age. This includes an increase in inflammation, and immunosenescence, the inability to efficiently respond to new immune challenges. These changes are evident in various diseases but have yet to be evaluated in a population with ischemic stroke. Age is an important factor in stroke, contributing to stroke risk, outcome and risk of hemorrhagic transformation. This study aimed to assess the changes that occur with age in the leukocyte gene expression of patients with ischemic stroke. Methods: Two cohorts of acute ischemic stroke patients were analyzed; cohort 1 (n=94) and cohort 2 (n=79). RNA was isolated from PAXgene tubes and processed on Affymetrix microarrays. Differentially expressed genes associated with age quartiles were identified by ANCOVA, adjusted for sex and batch. Functional analysis identified age-associated pathways. Differentially expressed genes were compared with previous non-stroke aging studies in whole blood. Results: There were 61 and 442 age-associated genes in cohorts 1 and 2 respectively (FDR-corrected p<0.05, partial correlation coefficient ≥ |0.3|). Nineteen genes, including CR2, CCR6 and CXCR5 , were found in common and decreased with age among both cohorts (max-log10(p value) = 17). Functional analysis of the 61 and 442 genes revealed with advancing age there is a change in the humoral immune system, including antibody production and B cell proliferation. When compared to aging gene expression studies in controls, 52% of age-associated genes in cohort 1 and 31% of cohort 2 age-associated genes overlapped with those found in controls, and 16 of the 19 common genes to both cohorts overlapped in controls (max-log10(p value) = 15). Conclusion: In patients with acute stroke there is a change in leukocyte gene expression with advancing age. Changes included a shift in humoral immune response with a potentially impaired B cell response. While many of the age-associated alterations in gene expression present in stroke are similar to non-stroke controls, these changes warrant further investigation for their impact on stroke outcome and risk.



2013 ◽  
Vol 45 (7) ◽  
pp. 276-286 ◽  
Author(s):  
Caroline G. Walker ◽  
Mathew D. Littlejohn ◽  
Susanne Meier ◽  
John R. Roche ◽  
Murray D. Mitchell

Coordinated regulation of endometrial gene expression is essential for successful pregnancy establishment. A nonreceptive uterine environment may be a key contributor to pregnancy loss, as the majority of pregnancy losses occur prior to embryo implantation. DNA methylation has been highlighted as a potential contributor in regulating early pregnancy events in the uterus. It was hypothesized that DNA methylation regulates expression of key genes in the uterus during pregnancy. The correlation between DNA methylation and gene expression was tested. Endometrial samples from fertile and subfertile dairy cow strains were obtained at day 17 of pregnancy or the reproductive cycle. Microarrays were used to characterize genome-wide DNA methylation profiles and data compared with previously published transcription profiles. 39% of DNA methylation probes assayed mapped to RefSeq genes with transcription measurements. Correlations among gene expression and DNA methylation were assessed, and the 1,000 most significant correlations used for subsequent analysis. Of these, 52% percent were negatively correlated with gene expression. When this gene list was compared with previously reported gene expression studies on the same tissues, 42% were differentially expressed when pregnant and cycling animals were compared, and 11% were differentially expressed when pregnant fertile and subfertile animals were compared. DNA methylation status was correlated with gene expression in several pathways implicated in early pregnancy events. Although these data do not provide direct evidence of a causative association between DNA methylation and gene expression, this study provides critical support for an effect of DNA methylation in early pregnancy events and highlights candidate genes for future studies.



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