scholarly journals Genes involved in conceptus–endometrial interactions in ruminants: insights from reductionism and thoughts on holistic approaches

Reproduction ◽  
2008 ◽  
Vol 135 (2) ◽  
pp. 165-179 ◽  
Author(s):  
Thomas E Spencer ◽  
Olivier Sandra ◽  
Eckhard Wolf
Keyword(s):  
Pregnancy Loss ◽  
Complex Dynamics ◽  
Transcriptional Profiling ◽  
Placental Lactogen ◽  
Physiological Models ◽  
Holistic Approaches ◽  
Expression Of Genes ◽  
Trophectoderm Cells ◽  
Improve Pregnancy Outcome ◽  
A Cell

This review summarizes new knowledge on expression of genes and provides insights into approaches for study of conceptus–endometrial interactions in ruminants with emphasis on the peri-implantation stage of pregnancy. Conceptus–endometrial interactions in ruminants are complex and involve carefully orchestrated temporal and spatial alterations in gene expression regulated by hormones from the ovary and conceptus. Progesterone is the hormone of pregnancy and acts on the uterus to stimulate blastocyst survival, growth, and development. Inadequate progesterone levels or a delayed rise in progesterone is associated with pregnancy loss. The mononuclear trophectoderm cells of the elongating blastocyst synthesize and secrete interferon-τ (IFNT), the pregnancy recognition signal. Trophoblast giant binucleate cells begin to differentiate and produce hormones including chorionic somatomammotropin 1 (CSH1 or placental lactogen). A number of genes, induced or stimulated by progesterone, IFNT, and/or CSH1 in a cell-specific manner, are implicated in trophectoderm adhesion to the endometrial luminal epithelium and regulation of conceptus growth and differentiation. Transcriptional profiling experiments are beginning to unravel the complex dynamics of conceptus–endometrial interactions in cattle and sheep. Future experiments should incorporate physiological models of pregnancy loss and be complemented by metabolomic studies of uterine lumen contents to more completely define factors required for blastocyst survival, growth, and implantation. Both reduction and holistic approaches will be important to understand the multifactorial phenomenon of recurrent pregnancy loss and provide a basis for new strategies to improve pregnancy outcome and reproductive efficiency in cattle and other domestic animals.

scholarly journals Chronicling the discovery of interferon tau

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. F11-F20 ◽  
Author(s):  
Fuller W Bazer ◽  
William W Thatcher
Keyword(s):  
Placental Lactogen ◽  
Corpora Lutea ◽  
Interferon Tau ◽  
Interferon Stimulated Genes ◽  
Expression Of Genes ◽  
Placental Growth Hormone ◽  
A Cell ◽  
Low Cytotoxicity ◽  
Conditioned Culture Medium ◽  
Uterine Glands

It has been 38 years since a protein, now known as interferon tau (IFNT), was discovered in ovine conceptus-conditioned culture medium. After 1979, purification and testing of native IFNT revealed its unique antiluteolyic activity to prevent the regression of corpora lutea on ovaries of nonpregnant ewes. Antiviral, antiproliferative and immunomodulatory properties of native and recombinant IFNT were demonstrated later. In addition, progesterone and IFNT were found to act cooperatively to silence expression of classical interferon stimulated genes in a cell-specific manner in ovine uterine luminal and superficial glandular epithelia. But, IFNT signaling through a STAT1/STAT2-independent pathway stimulates expression of genes, such as those for transport of glucose and amino acids, which are required for growth and development of the conceptus. Further, undefined mechanisms of action of IFNT are key to a servomechanism that allows ovine placental lactogen and placental growth hormone to affect the development of uterine glands and their expression of genes throughout gestation. IFNT also acts systemically to induce the expression of interferon stimulated genes that influence secretion of progesterone by the corpus luteum. Finally, IFNT has great potential as a therapeutic agent due to its low cytotoxicity, anti-inflammatory properties and effects to mitigate diabetes, obesity-associated syndromes and various autoimmune diseases.

scholarly journals An Antifungal Benzimidazole Derivative Inhibits Ergosterol Biosynthesis and Reveals Novel Sterols

2015 ◽  
Vol 59 (10) ◽  
pp. 6296-6307 ◽  
Author(s):  
Petra Keller ◽  
Christoph Müller ◽  
Isabel Engelhardt ◽  
Ekkehard Hiller ◽  
Karin Lemuth ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Fungal Infections ◽  
Transcriptional Profiling ◽  
Benzimidazole Derivative ◽  
Benzimidazole Derivatives ◽  
Ergosterol Biosynthesis ◽  
Screening Assay ◽  
Content Type ◽  
Life Threatening ◽  
A Cell

ABSTRACTFungal infections are a leading cause of morbidity and death for hospitalized patients, mainly because they remain difficult to diagnose and to treat. Diseases range from widespread superficial infections such as vulvovaginal infections to life-threatening systemic candidiasis. For systemic mycoses, only a restricted arsenal of antifungal agents is available. Commonly used classes of antifungal compounds include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapies, significant side effects, and high costs for several antifungals, there is a need for new antifungals in the clinic. In order to expand the arsenal of compounds with antifungal activity, we previously screened a compound library using a cell-based screening assay. A set of novel benzimidazole derivatives, including (S)-2-(1-aminoisobutyl)-1-(3-chlorobenzyl)benzimidazole (EMC120B12), showed high antifungal activity against several species of pathogenic yeasts, includingCandida glabrataandCandida krusei(species that are highly resistant to antifungals). In this study, comparative analysis of EMC120B12 versus fluconazole and nocodazole, using transcriptional profiling and sterol analysis, strongly suggested that EMC120B12 targets Erg11p in the ergosterol biosynthesis pathway and not microtubules, like other benzimidazoles. In addition to the marker sterol 14-methylergosta-8,24(28)-dien-3β,6α-diol, indicating Erg11p inhibition, related sterols that were hitherto unknown accumulated in the cells during EMC120B12 treatment. The novel sterols have a 3β,6α-diol structure. In addition to the identification of novel sterols, this is the first time that a benzimidazole structure has been shown to result in a block of the ergosterol pathway.

scholarly journals Trophectoderm-Specific Knockdown of LIN28 Decreases Expression of Genes Necessary for Cell Proliferation and Reduces Elongation of Sheep Conceptus

2020 ◽  
Vol 21 (7) ◽  
pp. 2549 ◽  
Author(s):  
Asghar Ali ◽  
Mark Stenglein ◽  
Thomas Spencer ◽  
Gerrit Bouma ◽  
Russell Anthony ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Critical Period ◽  
In Vitro Experiments ◽  
Placental Development ◽  
Expression Of Genes ◽  
Trophectoderm Cells ◽  
Successful Establishment

LIN28 inhibits let-7 miRNA maturation which prevents cell differentiation and promotes proliferation. We hypothesized that the LIN28-let-7 axis regulates proliferation-associated genes in sheep trophectoderm in vivo. Day 9-hatched sheep blastocysts were incubated with lentiviral particles to deliver shRNA targeting LIN28 specifically to trophectoderm cells. At day 16, conceptus elongation was significantly reduced in LIN28A and LIN28B knockdowns. Let-7 miRNAs were significantly increased and IGF2BP1-3, HMGA1, ARID3B, and c-MYC were decreased in trophectoderm from knockdown conceptuses. Ovine trophoblast (OTR) cells derived from day 16 trophectoderm are a useful tool for in vitro experiments. Surprisingly, LIN28 was significantly reduced and let-7 miRNAs increased after only a few passages of OTR cells, suggesting these passaged cells represent a more differentiated phenotype. To create an OTR cell line more similar to day 16 trophectoderm we overexpressed LIN28A and LIN28B, which significantly decreased let-7 miRNAs and increased IGF2BP1-3, HMGA1, ARID3B, and c-MYC compared to control. This is the first study showing the role of the LIN28-let-7 axis in trophoblast proliferation and conceptus elongation in vivo. These results suggest that reduced LIN28 during early placental development can lead to reduced trophoblast proliferation and sheep conceptus elongation at a critical period for successful establishment of pregnancy.

scholarly journals Transcriptional Profiling of Cholinergic Neurons From Basal Forebrain Identifies Changes in Expression of Genes Between Sleep and Wake

SLEEP ◽  
2017 ◽  
Vol 40 (6) ◽  
Author(s):  
Elena V. Nikonova ◽  
Jason DA Gilliland ◽  
Keith Q. Tanis ◽  
Alexei A. Podtelezhnikov ◽  
Alison M Rigby ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Transcriptional Profiling ◽  
Cholinergic Neurons ◽  
Expression Of Genes

scholarly journals INCREASE IN HSP25 EXTENDS LIFESPAN AND IMPROVES RESPONSE TO TAU TOXICITY THROUGH A CELL, NON-AUTONOMOUS MECHANISM

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S730-S730
Author(s):  
Karl Rodriguez
Keyword(s):  
Stress Response ◽  
Protein Aggregation ◽  
Cell Types ◽  
Over Expression ◽  
C Elegans ◽  
Expression Of Genes ◽  
Stress Response Pathway ◽  
A Cell ◽  
Cytotoxic Proteins ◽  
Improve Health

Abstract The accrual of aggregation-prone cytotoxic proteins underlies neural pathologies seen in aging, Alzheimer’s disease and other dementias. Recent evidence indicates that heat shock protein 25kDa (HSP25) interacts with tau. To demonstrate a causal role for HSP25 in these pathologies, we overexpressed HSP25 protein in worms. This manipulation led to an increase in life span. Moreover, the longevity-effect was associated with increased expression of genes downstream of the SKN-1/Nrf2 stress-response transcription factor. HSP25 over-expression also reduces aggregate pathology and extends lifespan in a C. elegans neuronal-specific, aggregate-prone tau model . We propose that over-expression of HSP25 could provide protection from protein aggregation induced neurodegeneration. However, it is not yet clear whether this HSP25 effect could be efficaciously provided exogenously by other cell types. Thus, we will test whether increased peripheral HSP25 will reduce protein aggregation and stimulate a global Skn-1 stress-response pathway, reduce toxicity in neurons, and improve health outcomes.

scholarly journals Dissecting Colony Development of Neurospora crassa Using mRNA Profiling and Comparative Genomics Approaches

2008 ◽  
Vol 7 (9) ◽  
pp. 1549-1564 ◽  
Author(s):  
Takao Kasuga ◽  
N. Louise Glass
Keyword(s):  
Neurospora Crassa ◽  
Transcriptional Profiling ◽  
Fundamental Aspect ◽  
Colony Development ◽  
Published Data ◽  
Middle Section ◽  
Data Set ◽  
Expression Of Genes ◽  
Spatiotemporal Regulation ◽  
Genetic Mechanisms

ABSTRACT Colony development, which includes hyphal extension, branching, anastomosis, and asexual sporulation, is a fundamental aspect of the life cycle of filamentous fungi; genetic mechanisms underlying these phenomena are poorly understood. We conducted transcriptional profiling during colony development of the model filamentous fungus Neurospora crassa, using 70-mer oligonucleotide microarrays. Relative mRNA expression levels were determined for six sections of defined age excised from a 27-h-old N. crassa colony. Functional category analysis showed that the expression of genes involved in cell membrane biosynthesis, polar growth, and cellular signaling was enriched at the periphery of the colony. The relative expression of genes involved in protein synthesis and energy production was enriched in the middle section of the colony, while sections of the colony undergoing asexual development (conidiogenesis) were enriched in expression of genes involved in protein/peptide degradation and unclassified proteins. A cross-examination of the N. crassa data set with a published data set of Aspergillus niger revealed shared patterns in the spatiotemporal regulation of gene orthologs during colony development. At present, less than 50% of genes in N. crassa have functional annotation, which imposes the chief limitation on data analysis. Using an evolutionary approach, we observed that the expression of phylogenetically conserved groups of genes was enriched in the middle section of an N. crassa colony whereas expression of genes unique to euascomycete species and of N. crassa orphan genes was enriched at the colony periphery and in the older, conidiating sections of a fungal colony.

scholarly journals Transcriptional Profiling of Target of RNAIII-Activating Protein, a Master Regulator of Staphylococcal Virulence

2005 ◽  
Vol 73 (10) ◽  
pp. 6220-6228 ◽  
Author(s):  
Moshe Korem ◽  
Yael Gov ◽  
Madanahally D. Kiran ◽  
Naomi Balaban
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Transcriptional Profiling ◽  
Protein A ◽  
Cell Communication ◽  
Global Regulator ◽  
Positive Bacterium ◽  
Master Regulator ◽  
Expression Of Genes ◽  
Histidine Phosphorylation

ABSTRACT Staphylococcus aureus is a gram-positive bacterium that is part of the normal healthy flora but that can become virulent and cause infections by producing biofilms and toxins. The production of virulence factors is regulated by cell-cell communication (quorum sensing) through the histidine phosphorylation of target of RNAIII-activating protein (TRAP), which is a 21-kDa protein that is highly conserved among staphylococci. Using microarray analysis, we show here that the expression and phosphorylation of TRAP upregulate the expression of most, if not all, toxins known to date, as well as their global regulator agr. In addition, we show here that the expression and phosphorylation of TRAP are also necessary for the expression of genes known to be necessary for the survival of the bacteria in a biofilm, like arc, pyr, and ure. TRAP is thus demonstrated to be a master regulator of staphylococcal pathogenesis.

Effects of agmatine on secretion of interferon tau and catecholamines and expression of genes related to production of polyamines by ovine trophectoderm cells

Amino Acids ◽  
2016 ◽  
Vol 48 (10) ◽  
pp. 2389-2399 ◽  
Author(s):  
Yasser Y. Lenis ◽  
Xiaoqiu Wang ◽  
Wanjin Tang ◽  
Guoyao Wu ◽  
Fuller W. Bazer
Keyword(s):  
Interferon Tau ◽  
Expression Of Genes ◽  
Trophectoderm Cells
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