scholarly journals Transcriptional activity of oestrogen receptors in the course of embryo development

2018 ◽  
Vol 238 (3) ◽  
pp. 165-176 ◽  
Author(s):  
Sara Della Torre ◽  
Gianpaolo Rando ◽  
Clara Meda ◽  
Paolo Ciana ◽  
Luisa Ottobrini ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Reproductive Organs ◽  
Luciferase Expression ◽  
Potential Contribution ◽  
Oestrogen Receptors ◽  
Mouse Development ◽  
Reporter Mouse ◽  
Proliferation And Differentiation ◽  
Differentiation Factors ◽  
Prenatal Effects

Oestrogens are well-known proliferation and differentiation factors that play an essential role in the correct development of sex-related organs and behaviour in mammals. With the use of the ERE-Luc reporter mouse model, we show herein that throughout mouse development, oestrogen receptors (ERs) are active starting from day 12 post conception. Most interestingly, we show that prenatal luciferase expression in each organ is proportionally different in relation to the germ layer of the origin. The luciferase content is highest in ectoderm-derived organs (such as brain and skin) and is lowest in endoderm-derived organs (such as liver, lung, thymus and intestine). Consistent with the testosterone surge occurring in male mice at the end of pregnancy, in the first 2 days after birth, we observed a significant increase in the luciferase content in several organs, including the liver, bone, gonads and hindbrain. The results of the present study show a widespread transcriptional activity of ERs in developing embryos, pointing to the potential contribution of these receptors in the development of non-reproductive as well as reproductive organs. Consequently, the findings reported here might be relevant in explaining the significant differences in male and female physiopathology reported by a growing number of studies and may underline the necessity for more systematic analyses aimed at the identification of the prenatal effects of drugs interfering with ER signalling, such as aromatase inhibitors or endocrine disrupter chemicals.

Gli2, but notGli1, is required for initial Shh signaling and ectopic activation of the Shh pathway

Development ◽  
2002 ◽  
Vol 129 (20) ◽  
pp. 4753-4761 ◽  
Author(s):  
C. Brian Bai ◽  
Wojtek Auerbach ◽  
Joon S. Lee ◽  
Daniel Stephen ◽  
Alexandra L. Joyner
Keyword(s):  
Signaling Pathway ◽  
Negative Regulator ◽  
Embryonic Patterning ◽  
Mouse Development ◽  
Shh Signaling ◽  
Shh Pathway ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mammalian Tissues ◽  
Ectopic Activation

The Shh signaling pathway is required in many mammalian tissues for embryonic patterning, cell proliferation and differentiation. In addition, inappropriate activation of the pathway has been implicated in many human tumors. Based on transfection assays and gain-of-function studies in frog and mouse, the transcription factor Gli1 has been proposed to be a major mediator of Shh signaling. To address whether this is the case in mouse, we generated a Gli1 null allele expressing lacZ. Strikingly, Gli1 is not required for mouse development or viability. Of relevance, we show that all transcription of Gli1 in the nervous system and limbs is dependent on Shh and, consequently, Gli1 protein is normally not present to transduce initial Shh signaling. To determine whether Gli1 contributes to the defects seen when the Shh pathway is inappropriately activated and Gli1 transcription is induced, Gli1;Ptc double mutants were generated. We show that Gli1 is not required for the ectopic activation of the Shh signaling pathway or to the early embryonic lethal phenotype in Ptc null mutants. Of significance, we found instead that Gli2 is required for mediating some of the inappropriate Shh signaling in Ptc mutants. Our studies demonstrate that, in mammals, Gli1 is not required for Shh signaling and that Gli2 mediates inappropriate activation of the pathway due to loss of the negative regulator Ptc.

scholarly journals Hypersensitivity to DNA damage leads to increased apoptosis during early mouse development

2000 ◽  
Vol 14 (16) ◽  
pp. 2072-2084
Author(s):  
Babette S. Heyer ◽  
Alasdair MacAuley ◽  
Ole Behrendtsen ◽  
Zena Werb
Keyword(s):  
Dna Damage ◽  
Cell Fate ◽  
Genotoxic Stress ◽  
Embryonic Cells ◽  
Mouse Development ◽  
Potential Cost ◽  
Proliferation And Differentiation ◽  
A Cell ◽  
Early Mouse ◽  
Surveillance Mechanism

Gastrulation in mice is associated with the start of extreme proliferation and differentiation. The potential cost to the embryo of a very rapid proliferation rate is a high production of damaged cells. We demonstrate a novel surveillance mechanism for the elimination of cells damaged by ionizing radiation during mouse gastrulation. During this restricted developmental window, the embryo becomes hypersensitive to DNA damage induced by low dose irradiation (<0.5 Gy) and undergoes apoptosis without cell cycle arrest. Intriguingly, embryonic cells, including germ cell progenitors, but not extraembryonic cells, become hypersensitive to genotoxic stress and undergo Atm- and p53-dependent apoptosis. Thus, hypersensitivity to apoptosis in the early mouse embryo is a cell fate-dependent mechanism to ensure genomic integrity during a period of extreme proliferation and differentiation.

Upregulation of signal transducer and activator of transcription 4 promotes osteoblast activity by activating AMP-activated protein kinase based on cationic liposome transfection

2020 ◽  
Vol 10 (11) ◽  
pp. 1836-1845
Author(s):  
Tao Jiang ◽  
Qingzhen Chen ◽  
Min Shao ◽  
Zhen Shen ◽  
Gang Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Osteogenic Differentiation ◽  
Transcriptional Activity ◽  
Cationic Liposome ◽  
Promoter Sequence ◽  
Fluorescence Quantitative Pcr ◽  
Osteoblast Activity ◽  
Activity Factor ◽  
Proliferation And Differentiation ◽  
Amp Activated Protein Kinase

Activation of Protein Kinase AMP-Activated Catalytic Subunit Alpha (AMPKα) is an important regulatory pathway for osteogenic differentiation. STAT4 acts as a transcriptional activity factor to regulate the transcription of many genes and is potentially a regulatory factor for AMPKα transcription activity. To confirm the regulatory effect of STAT4 on AMPKα and the effect of STAT4 on osteogenic differentiation, the promoter sequence of AMPKα was analyzed via bioinformatics, the STAT4 overexpression vector was constructed and transfected into human osteoblast-like cells MG-63 by cationic liposome, fluorescence quantitative PCR (RT-qPCR) and western blotting technologies were used to detect the effect of STAT4 on the expression of AMPKα. MTT and ALP activity assays were also used to verify the effect of STAT4 on the proliferation and maturation of osteoblasts by regulating AMPKα expression. Our results showed that STAT4 was a co-transcriptional regulator of AMPKα1 and AMPKα2, which combined the enrichment region of CpG on the promoter sequence of AMPKα1/2. Overexpression of STAT4 significantly increased the expression of AMPKα1 and AMPKα2, which promoted the proliferation and maturation of osteoblasts. We concluded that STAT4 was a transcriptional activator of AMPKα and promoting STAT4 expression enhances the proliferation and differentiation activity of AMPKα in osteoblasts.

scholarly journals Stromal cell-derived factor: pathological and clinical potentialities

2020 ◽  
Vol 3 (3) ◽  
pp. 198-204
Author(s):  
O.V. Prokhorova ◽  
◽  
A.A. Olina ◽  
G.Kh. Tolibova ◽  
T.G. Tral’ ◽  
...  
Keyword(s):  
Stromal Cell ◽  
Reproductive Organs ◽  
Published Data ◽  
Clear Understanding ◽  
Leading Role ◽  
Placental Angiogenesis ◽  
Proliferation And Differentiation ◽  
Uterine Mucosa ◽  
Stromal Cell Derived Factor ◽  
Homeostatic Cytokines

Chemotactic cytokines are a family of signaling proteins secreted by various human tissues. Their functioning is based on the ability to induce directed chemotaxis in nearby susceptible cells. This paper reviews recent published data on one of the most important homeostatic cytokines, stromal cell-derived factor-1 (SDF-1). The leading role of this factor in the pathogenesis of various conditions, i.e., toxic, ischemic, and necrotic tissue damage, carcinogenesis (including the mechanisms of invasion and metastasis) is demonstrated. SDF-1 acts as a powerful inductor of angiogenesis and stimulates the proliferation of endothelial cells in reproductive organs. This chemokine is one of the candidate factors involved in the regulation of proliferation and differentiation of human endometrium, i.e., the implementation of epithelial-stromal interaction of tissue elements in uterine mucosa. Clear understanding of the regulatory mechanisms of SDF-1-mediated signaling during trophoblast functioning and placental angiogenesis may help develop novel therapeutic approaches to pregnancy-related disorders.KEYWORDS: stromal cell-derived factor, chemokines, cytokines, pathogenesis, pregnancy, homeostasis.FOR CITATION: Prokhorova O.V., Olina A.A., Tolibova G.Kh., Tral’ T.G. Stromal cell-derived factor: pathological and clinical potentialities. Russian Journal of Woman and Child Health. 2020;3(3):198–204. DOI: 10.32364/2618-8430-2020-3-3-198-204.

scholarly journals Comprehensive Analysis of Human Endogenous Retrovirus Transcriptional Activity in Human Tissues with a Retrovirus-Specific Microarray

2005 ◽  
Vol 79 (1) ◽  
pp. 341-352 ◽  
Author(s):  
Wolfgang Seifarth ◽  
Oliver Frank ◽  
Udo Zeilfelder ◽  
Birgit Spiess ◽  
Alex D. Greenwood ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Activity Patterns ◽  
Qualitative Evaluation ◽  
Reproductive Organs ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Human Tissues ◽  
Human Endogenous Retroviruses ◽  
Transcriptional Regulatory

ABSTRACT Retrovirus-like sequences account for 8 to 9% of the human genome. Among these sequences, about 8,000 pol-containing proviral elements have been identified to date. As part of our ongoing search for active and possibly disease-relevant human endogenous retroviruses (HERVs), we have recently developed an oligonucleotide-based microarray. The assay allows for both the detection and the identification of most known retroviral reverse transcriptase (RT)-related nucleic acids in biological samples. In the present study, we have investigated the transcriptional activity of representative members of 20 HERV families in 19 different normal human tissues. Qualitative evaluation of chip hybridization signals and quantitative analysis by real-time RT-PCR revealed distinct HERV activity in the human tissues under investigation, suggesting that HERV elements are active in human cells in a tissue-specific manner. Most active members of HERV families were found in mRNA prepared from skin, thyroid gland, placenta, and tissues of reproductive organs. In contrast, only few active HERVs were detectable in muscle cells. Human tissues that lack HERV transcription could not be found, confirming that human endogenous retroviruses are permanent components of the human transcriptome. Distinct activity patterns may reflect the characteristics of the regulatory machinery in these cells, e.g., cell type-dependent occurrence of transcriptional regulatory factors.

scholarly journals Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4.

1997 ◽  
Vol 17 (9) ◽  
pp. 5338-5347 ◽  
Author(s):  
E Neuman ◽  
M H Ladha ◽  
N Lin ◽  
T M Upton ◽  
S J Miller ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cyclin D1 ◽  
Transcriptional Activity ◽  
Ectopic Expression ◽  
Normal Breast ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Specific Complex ◽  
Stimulation Of

Cyclin D1 plays an important role in the development of breast cancer and is required for normal breast cell proliferation and differentiation associated with pregnancy. We show that ectopic expression of cyclin D1 can stimulate the transcriptional activity of the estrogen receptor in the absence of estradiol and that this activity can be inhibited by 4-hydroxytamoxifen and ICI 182,780. Cyclin D1 can form a specific complex with the estrogen receptor. Stimulation of the estrogen receptor by cyclin D1 is independent of cyclin-dependent kinase 4 activation. Cyclin D1 may manifest its oncogenic potential in breast cancer in part through binding to the estrogen receptor and activation of the transcriptional activity of the receptor.

Content of retinol and retinyl esters in blood plasma, liver, kidney and reproductive organs of Japanese quails

2002 ◽  
Vol 50 (4) ◽  
pp. 435-443 ◽  
Author(s):  
Annamária Kerti ◽  
Ingeborg Buchholz ◽  
F. J. Schweigert
Keyword(s):  
Vitamin A ◽  
Blood Plasma ◽  
Reproductive Organs ◽  
Egg Laying ◽  
Dominant Form ◽  
Physiological Processes ◽  
Egg Formation ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Retinyl Esters

Due to its importance in many physiological processes such as cell proliferation and differentiation, vitamin A plays a key role in reproduction. The present study examines the content and distribution of retinol and retinyl esters in the blood plasma, liver, kidney, ovary and oviduct (infundibulum, magnum, isthmus and uterus) of the laying Japanese quail. (1) The results show that the stage of egg laying had no influence on the level of vitamin A (retinol or retinyl esters) in plasma, kidney and liver. (2) The results further indicate that in the oviduct there are quantitative and qualitative differences in the concentration of retinol and retinyl esters, but that these differences are not altered by the stage of egg formation. (3) The highest levels of vitamin A in the isthmus and uterus were associated with a predominance of retinyl esters (palmitate and stearate); sections with lower total levels of vitamin A (infundibulum, magnum) had retinol as the more dominant form of vitamin A. (4) Changes in the ratio of retinol to retinyl esters in the various sections of the avian oviduct might point to metabolic differences. The storage of vitamin A might therefore be the predominant function of the uterus and isthmus; in the infundibulum and magnum, where vitamin A is predominantly present as retinol, vitamin A serves rather as a precursor for the modulation of the cellular metabolism of these structures.

The biogenesis of the coiled body during early mouse development

Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 601-612 ◽  
Author(s):  
J. Ferreira ◽  
M. Carmo-Fonseca
Keyword(s):  
Mammalian Cells ◽  
Transcriptional Activity ◽  
Nucleolar Protein ◽  
Electron Microscopic Level ◽  
Fibrillar Structure ◽  
Coiled Body ◽  
Mouse Development ◽  
Coiled Bodies ◽  
Essential Components ◽  
Early Mouse

The coiled body is an ubiquitous nuclear organelle that contains essential components of the pre-mRNA splicing machinery as well as the nucleolar protein fibrillarin. Here we have studied the biogenesis of the coiled body in early mouse embryos. The results show that coiled bodies form and concentrate splicing snRNPs as early as in the maternal and paternal pronuclei of 1-cell embryos. This argues that the coiled body is likely to play a basic role in the nucleus of mammalian cells. In order to correlate the appearance of coiled bodies with the onset of transcriptional activity, embryos were incubated with brominated UTP and the incorporated nucleotide was visualized by fluorescence microscopy. In agreement with previous studies, transcriptional activity was first observed during the 2-cell stage. Thus, coiled bodies form before activation of embryonic gene expression. The appearance of coiled bodies in 1-cell embryos was preceded by the formation of morphologically distinct structures that also contain coilin and which we therefore refer to as pre-coiled bodies. At the electron microscopic level pre-coiled bodies have a compact fibrillar structure, whereas coiled bodies resemble a tangle of coiled threads. Although both pre-coiled bodies and coiled bodies contain the nucleolar protein fibrillarin, the assembly of coiled bodies is separated both in time and in space from ribosome synthesis. Our results suggest that the embryonic ‘nucleolus-like body’ is a structural scaffold that nucleates independently the formation of the coiled body and the assembly of the machinery responsible for ribosome biosynthesis.

scholarly journals Activity of Retinoic Acid Receptor-alpha Is Directly Regulated at Its Protein Kinase A Sites in Response to Follicle-Stimulating Hormone Signaling

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2361-2372 ◽  
Author(s):  
Nadine C. Santos ◽  
Kwan Hee Kim
Keyword(s):  
Cell Proliferation ◽  
Retinoic Acid ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Nuclear Localization ◽  
Transcriptional Activity ◽  
Retinoic Acid Receptor ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Kinase A

Retinoic acid receptor-α (RARA) is crucial for germ cell development in the testis, as shown by the degenerated testis in Rara gene knockout mice, which are sterile. Similarly, FSH is known to regulate Sertoli cell proliferation and differentiation, indirectly controlling the quantity of the spermatogenic output. Interestingly, FSH inhibited, via activation of FSH receptor, cAMP, and protein kinase A (PKA), the nuclear localization and transcriptional activity of RARA. Given that retinoic acid, the ligand for RARA, is known to regulate cell proliferation and differentiation, we investigated whether FSH regulates RARA by a direct posttranslational phosphorylation mechanism. Mutagenesis of serine 219 (S219) and S369 at the PKA sites on RARA to either double alanines or double glutamic acids showed that both PKA sites are important for RARA activity. The negative charges at the PKA sites, whether they are from glutamic acids or phosphorylation of serines, decreased the nuclear localization of RARA, heterodimerization with retinoid X receptor-α, and the transcriptional activity of the receptor. On the other hand, the double-alanine mutant that cannot be phosphorylated at the 219 and 369 amino acid positions did not respond to cAMP and PKA activation. Wild-type and double-mutant RARA interacted with PKA, but only in the presence of cAMP or FSH. These results together suggest that FSH may regulate cell proliferation and differentiation of Sertoli cells, at least partially, by directly affecting the PKA sites of RARA and controlling the transcriptional function of the receptor.

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