scholarly journals Cyclooxygenase and prostaglandins in somatic cell populations of the testis

Reproduction ◽  
2015 ◽  
Vol 149 (4) ◽  
pp. R169-R180 ◽  
Author(s):  
Mónica B Frungieri ◽  
Ricardo S Calandra ◽  
Artur Mayerhofer ◽  
María E Matzkin
Keyword(s):  
Somatic Cell ◽  
Sertoli Cells ◽  
Cell Types ◽  
Therapeutic Approaches ◽  
Link Type ◽  
New Therapeutic Approaches ◽  
Rate Limiting ◽  
Cox2 Expression ◽  
Tubule Wall ◽  
Testicular Inflammation

Prostaglandins (PGs) are synthesized through the action of the rate-limiting enzyme cyclooxygenase (COX) and further specific enzymes. The development ofCox-deficient mice in the 1990s gave insights into the reproductive roles of PGs. FemaleCox-knockout mice were subfertile or infertile. Interestingly, fertility was not affected in male mice deficient inCox, suggesting that PGs may not be critical for the functioning of the testis. However, this conclusion has recently been challenged by observations of important roles for PGs in both physiological and pathological processes in the testis. The two key somatic cell types in the testis, Leydig and Sertoli cells, express the inducible isoenzyme COX2 and produce PGs. Testicular COX2 expression in these somatic cells is regulated by hormonal input (FSH, prolactin (PRL), and testosterone) as well as by IL1β. PGs modulate steroidogenesis in Leydig cells and glucose uptake in Sertoli cells. Hence, the COX2/PG system in Leydig and Sertoli cells acts as a local modulator of testicular activity, and consequently may regulate spermatogenic efficiency. In addition to its expression in Leydig and Sertoli cells, COX2 has been detected in the seminiferous tubule wall, and in testicular macrophages and mast cells of infertile patients. These observations highlight the possible relevance of PGs in testicular inflammation associated with idiopathic infertility. Collectively, these data indicate that the COX2/PG system plays crucial roles not only in testicular physiology (i.e., development, steroidogenesis, and spermatogenesis), but more importantly in the pathogenesis or maintenance of infertility status in the male gonad. Further studies of these actions could lead to new therapeutic approaches to idiopathic male infertility.Free German abstractA German translation of this abstract is freely available athttp://www.reproduction-online.org/content/149/4/R169/suppl/DC1.Free Spanish abstractA Spanish translation of this abstract is freely available athttp://www.reproduction-online.org/content/149/4/R169/suppl/DC2.

scholarly journals Reprogramming of Sertoli cells to fetal-like Leydig cells by Wt1 ablation

2015 ◽  
Vol 112 (13) ◽  
pp. 4003-4008 ◽  
Author(s):  
Lianjun Zhang ◽  
Min Chen ◽  
Qing Wen ◽  
Yaqiong Li ◽  
Yaqing Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Somatic Cell ◽  
Progenitor Cells ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Gonad Development ◽  
Cell Types ◽  
Lineage Tracing ◽  
Specific Gene

Sertoli and Leydig cells, the two major somatic cell types in the testis, have different morphologies and functions. Both are essential for gonad development and spermatogenesis. However, whether these cells are derived from the same progenitor cells and the mechanism regulating the differentiation between these two cell types during gonad development remains unclear. A previous study showed that overactivation of Ctnnb1 (cadherin-associated protein, beta 1) in Sertoli cells resulted in Sertoli cell tumors. Surprisingly, in the present study, we found that simultaneous deletion of Wilms’ Tumor Gene 1 (Wt1) and overactivation of Ctnnb1 in Sertoli cells led to Leydig cell-like tumor development. Lineage tracing experiments revealed that the Leydig-like tumor cells were derived from Sertoli cells. Further studies confirmed that Wt1 is required for the maintenance of the Sertoli cell lineage and that deletion of Wt1 resulted in the reprogramming of Sertoli cells to Leydig cells. Consistent with this interpretation, overexpression of Wt1 in Leydig cells led to the up-regulation of Sertoli cell-specific gene expression and the down-regulation of steroidogenic gene expression. These results demonstrate that the distinction between Sertoli cells and Leydig cells is regulated by Wt1, implying that these two cell types most likely originate from the same progenitor cells. This study thus provides a novel concept for somatic cell fate determination in testis development that may also represent an etiology of male infertility in human patients.

scholarly journals Adrenal glands stem cells: general signaling pathways

2021 ◽  
Vol 67 (6) ◽  
pp. 90-97
Author(s):  
O. V. Glazova ◽  
M. V. Vorontsova ◽  
L. V. Shevkova ◽  
N. Sakr ◽  
N. A. Onyanov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adrenal Gland ◽  
Signaling Pathways ◽  
Cell Types ◽  
Patient Specific ◽  
Therapeutic Approaches ◽  
Adult Type ◽  
New Therapeutic Approaches ◽  
Induced Pluripotent

 Nowadays stem cells of adult type are attractive in case of active development of cell and genome technologies. They are the target of new therapeutic approaches, which are based on correction of mutations or replenishment of organs, that were damaged by autoimmune reactions, aging or other pathological processes. Also stem cells, including patient-specific (induced Pluripotent Stem Cells, iPSCs), and obtained by differentiation from them tissue cultures and organoids are the closest models to in vivo researches on humans, which gives an opportunity to get more relevant data while testing different therapeutic approaches and pharmacological drugs. The main molecular pathways, that are essential for homeostasis of a cortex of a adrenal gland — compound, structurally and functionally heterogeneous organ, is described the presented review. The adrenal cortex is renewing during the organism’s ontogenesis at the expense of the pool of stem and progenitors cells, which are in tight junctions with differentiated steroidogenic cells and which are under constant control of endocrine and paracrine signals. The understanding of signaling pathways and interactions of different cell types will give an opportunity to develop the most suitable protocols for obtaining cells of adrenal gland cortex in a different stages of differentiation to use them in scientific and medical purposes. 

scholarly journals Promising PEGylated cationic dendrimers for delivery of miRNAs as a possible therapy against HIV-1 infection

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
E. Royo-Rubio ◽  
I. Rodríguez-Izquierdo ◽  
M. Moreno-Domene ◽  
T. Lozano-Cruz ◽  
F. J. de la Mata ◽  
...  
Keyword(s):  
Cell Types ◽  
Delivery Systems ◽  
Target Cells ◽  
Therapeutic Approaches ◽  
Rna Molecules ◽  
New Therapeutic Approaches ◽  
Efficient Delivery ◽  
Effective Delivery ◽  
New Treatments ◽  
Hiv 1

Abstract Background The appearance of resistance against new treatments and the fact that HIV-1 can infect various cell types and develop reservoirs and sanctuaries makes it necessary to develop new therapeutic approaches to overcome those failures. Results Studies of cytotoxicity, genotoxicity, complexes formation, stability, resistance, release and particle size distribution confirmed that G2-SN15-PEG, G3-SN31-PEG, G2-SN15-PEG-FITC and G3-SN31-PEG-FITC dendrimers can form complexes with miRNAs being biocompatible, stable and conferring protection to these nucleic acids. Confocal microscopy and flow cytometry showed effective delivery of these four dendrimers into the target cells, confirming their applicability as delivery systems. Dendriplexes formed with the dendrimers and miRNAs significantly inhibited HIV-1 infection in PBMCs. Conclusions These dendrimers are efficient delivery systems for miRNAs and they specifically and significantly improved the anti-R5-HIV-1 activity of these RNA molecules. Graphic Abstract

scholarly journals sCD28, sCD80, sCTLA-4, and sBTLA Are Promising Markers in Diagnostic and Therapeutic Approaches for Aseptic Loosening and Periprosthetic Joint Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Jil M. Jubel ◽  
Thomas M. Randau ◽  
Janine Becker-Gotot ◽  
Sebastian Scheidt ◽  
Matthias D. Wimmer ◽  
...  
Keyword(s):  
Aseptic Loosening ◽  
Immune Cell ◽  
Joint Infection ◽  
Cell Types ◽  
Quantitative Composition ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Joint Infections ◽  
Significant Difference ◽  
Prosthetic Loosening

Aseptic prosthetic loosening and periprosthetic joint infections (PJI) are among the most frequent complications after total knee/hip joint arthroplasty (TJA). Current research efforts focus on understanding the involvement of the immune system in these frequent complications. Different immune cell types have already been implicated in aseptic prosthetic loosening and PJI. The aim of this study was to systematically analyze aspirates from knee and hip joints, evaluating the qualitative and quantitative composition of soluble immunoregulatory markers, with a focus on co-inhibitory and co-stimulatory markers. It has been shown that these molecules play important roles in immune regulation in cancer and chronic infectious diseases, but they have not been investigated in the context of joint replacement. For this purpose, aspirates from control joints (i.e., native joints without implanted prostheses), joints with TJA (no signs of infection or aseptic loosening), joints with aseptic implant failure (AIF; i.e., aseptic loosening), and joints with PJI were collected. Fourteen soluble immunoregulatory markers were assessed using bead-based multiplex assays. In this study, it could be shown that the concentrations of the analyzed immunoregulatory molecules vary between control, TJA, AIF, and PJI joints. Comparing TJA patients to CO patients, sCD80 was significantly elevated. The marker sBTLA was significantly elevated in AIF joints compared to TJA joints. In addition, a significant difference for eight markers could be shown when comparing the AIF and CO groups (sCD27, sCTLA-4, sCD137, sCD80, sCD28, sTIM-3, sPD-1, sBTLA). A significant difference was also reached for nine soluble markers when the PJI and CO groups were compared (sLAG-3, sCTLA-4, sCD27, sCD80, sCD28, sTIM-3, sPD-1, IDO, sBTLA). In summary, the analyzed immunoregulatory markers could be useful for diagnostic purposes as well as to develop new therapeutic approaches for AIF and PJI.

In situ analysis of fetal, prepuberal and adult XX—XY chimaeric mouse testes: Sertoli cells are predominantly, but not exclusively, XY

Development ◽  
1991 ◽  
Vol 112 (1) ◽  
pp. 265-268 ◽  
Author(s):  
S.J. Palmer ◽  
P.S. Burgoyne
Keyword(s):  
Somatic Cell ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
In Situ Hybridisation ◽  
Age Groups ◽  
Cell Types ◽  
Beta Globin ◽  
Cell Type ◽  
Cell Lineages

The testes of fetal, prepuberal and adult XX—XY chimaeras were examined using in situ hybridisation to identify the beta-globin transgenic marker contained in one component of each chimaera. This enabled the proportion of XX and XY cells contributing to the major cell lineages of the testis to be estimated from sectioned and air-dried material. A few XX Sertoli cells were found in all three age groups, but the XX contribution was always much lower than in other somatic cell types. Significantly, in fetal XX—XY testes, Sertoli cells were the only cell type to show a bias in favour of the XY component. This strengthens the view that Tdy acts solely in the lineage that gives rise to Sertoli cells. However, the finding of some fetal XX Sertoli cells means that one of the steps in the Tdy-initiated process of Sertoli cell determination is capable of locally recruiting XX cells.

Annulate lamellae in the Sertoli cells of guinea pig testis after unilateral torsion of the spermatic cord

1984 ◽  
Vol 42 ◽  
pp. 196-197
Author(s):  
J. Chakraborty ◽  
A. P. Sinha Hikim ◽  
J. S. Jhunjhunwala
Keyword(s):  
Sertoli Cells ◽  
Guinea Pigs ◽  
Spermatic Cord ◽  
Present Report ◽  
Cell Types ◽  
Annulate Lamellae ◽  
Spermatogenic Cells ◽  
Electron Microscopic ◽  
Structural Details ◽  
First Time

Although the presence of annulate lamellae was noted in many cell types, including the rat spermatogenic cells, this structure was never reported in the Sertoli cells of any rodent species. The present report is based on a part of our project on the effect of torsion of the spermatic cord to the contralateral testis. This paper describes for the first time, the fine structural details of the annulate lamellae in the Sertoli cells of damaged testis from guinea pigs.One side of the spermatic cord of each of six Hartly strain adult guinea pigs was surgically twisted (540°) under pentobarbital anesthesia (1). Four months after induction of torsion, animals were sacrificed, testes were excised and processed for the light and electron microscopic investigations. In the damaged testis, the majority of seminiferous tubule contained a layer of Sertoli cells with occasional spermatogonia (Fig. 1). Nuclei of these Sertoli cells were highly pleomorphic and contained small chromatinic clumps adjacent to the inner aspect of the nuclear envelope (Fig. 2).

Nanotheranostic agents for neurodegenerative diseases

2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Cell Types ◽  
Specific Cell ◽  
Ageing Population ◽  
Target Tissue ◽  
Therapeutic Approaches ◽  
Surface Receptors ◽  
Theranostic Agents ◽  
Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

New therapeutic approaches for polymyositis and dermatomyositis

2011 ◽  
Vol 152 (39) ◽  
pp. 1552-1559 ◽  
Author(s):  
Katalin Dankó ◽  
Melinda Vincze
Keyword(s):  
Immunosuppressive Agents ◽  
Inflammatory Myopathy ◽  
Proximal Muscle ◽  
Therapeutic Approaches ◽  
First Line ◽  
New Therapeutic Approaches ◽  
Remission Period ◽  
Immune Mediated ◽  
Systemic Manifestations ◽  
Line Of Therapy

Inflammatory myopathies are chronic, immune-mediated diseases characterized with progressive proximal muscle weakness. They encompass a variety of syndromes with protean manifestations. The aims of therapy are to increase muscle strength, prevent the development of contractures, and to manage the systemic manifestations of the disease. This is a complex treatment which requires routine and wide knowledge. The most important task is to recognize the disease and guide the patient to immunologic center. Although the first line of therapy continues to include corticosteroids, there are a multitude of agents available for treating patients with myositis. There are several different immunosuppressive agents which may be applied alone or in combination with each other, as well as an increasing number of novel and exciting biologic agents targeting molecules participating in the pathogenesis of inflammatory myopathy. Physiotherapy and rehabilitation in the remission period may significantly improve the functional outcome of patients with these disorders. Orv. Hetil., 2011, 152, 1552–1559.

scholarly journals New Aspects of the Epigenetics of Pancreatic Carcinogenesis

Epigenomes ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 18
Author(s):  
Murat Toruner ◽  
Martin E. Fernandez-Zapico ◽  
Christopher L. Pin
Keyword(s):  
Pancreatic Cancer ◽  
Dna Methylation ◽  
Survival Rate ◽  
Epigenetic Mechanisms ◽  
Therapeutic Approaches ◽  
Cancer Epigenetics ◽  
Pancreatic Carcinogenesis ◽  
New Therapeutic Approaches ◽  
Environmental Events ◽  
Underlying Pathogenesis

Pancreatic cancer remains among the deadliest forms of cancer with a 5 year survival rate less than 10%. With increasing numbers being observed, there is an urgent need to elucidate the pathogenesis of pancreatic cancer. While both contribute to disease progression, neither genetic nor environmental factors completely explain susceptibility or pathogenesis. Defining the links between genetic and environmental events represents an opportunity to understand the pathogenesis of pancreatic cancer. Epigenetics, the study of mitotically heritable changes in genome function without a change in nucleotide sequence, is an emerging field of research in pancreatic cancer. The main epigenetic mechanisms include DNA methylation, histone modifications and RNA interference, all of which are altered by changes to the environment. Epigenetic mechanisms are being investigated to clarify the underlying pathogenesis of pancreatic cancer including an increasing number of studies examining the role as possible diagnostic and prognostic biomarkers. These mechanisms also provide targets for promising new therapeutic approaches for this devastating malignancy.

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