scholarly journals High Throughput scRNA-Seq Provides Insights Into Leydig Cell Senescence Induced by Experimental Autoimmune Orchitis: A Prominent Role of Interstitial Fibrosis and Complement Activation

2022 ◽  
Vol 12 ◽  
Author(s):  
Yinchuan Li ◽  
Panpan Mi ◽  
Jiabao Wu ◽  
Yunge Tang ◽  
Xiaohua Liu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
High Throughput ◽  
Interstitial Fibrosis ◽  
Glutathione Metabolism ◽  
Seminiferous Tubules ◽  
Sex Characteristics ◽  
Androgen Synthesis ◽  
Chemokine Signaling ◽  
Autoimmune Orchitis ◽  
Experimental Autoimmune

Leydig cells (Lc), located in the interstitial space of the testis between seminiferous tubules, produce 95% of testosterone in male individuals, which is pivotal for male sexual differentiation, spermatogenesis, and maintenance of the male secondary sex characteristics. Lc are prone to senescence in aging testes, resulting in compromised androgen synthesis capability upon aging. However, little is known about whether Lc undergo senescence in a chronic inflammatory environment. To investigate this question, mouse models of experimental autoimmune orchitis (EAO) were used, and Lc were analyzed by high throughput scRNA-Seq. Data were screened and analyzed by correlating signaling pathways with senescence, apoptosis, androgen synthesis, and cytokine/chemokine signaling pathways. EAO did induce Lc senescence, and Lc senescence in turn antagonized androgen synthesis. Based on the correlation screening of pathways inducing Lc senescence, a plethora of pathways were found to play potential roles in triggering Lc senescence during EAO, among which the Arf6 and angiopoietin receptor pathways were highly correlated with senescence signature. Notably, complement and interstitial fibrosis activated by EAO worsened Lc senescence and strongly antagonized androgen synthesis. Furthermore, most proinflammatory cytokines enhanced both senescence and apoptosis in Lc and spermatogonia (Sg) during EAO, and proinflammatory cytokine antagonism of the glutathione metabolism pathway may be key in inducing cellular senescence during EAO.

scholarly journals Involvement of CD44 in leukocyte recruitment to the rat testis in experimental autoimmune orchitis

Reproduction ◽  
2005 ◽  
Vol 129 (5) ◽  
pp. 603-609 ◽  
Author(s):  
V A Guazzone ◽  
B Denduchis ◽  
L Lustig
Keyword(s):  
Fluorescence Intensity ◽  
Mean Fluorescence Intensity ◽  
Mononuclear Cells ◽  
Leukocyte Recruitment ◽  
Seminiferous Tubules ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Peripheral Blood Mononuclear ◽  
Autoimmune Orchitis ◽  
Experimental Autoimmune

Experimental autoimmune orchitis (EAO) is characterized by an interstitial mononuclear cell infiltrate and a severe lesion of the seminiferous tubules with germ cells that undergo apoptosis and sloughing. The aim of this study was to determine the role of CD44 in testicular leukocyte recruitment in EAO. The biological functions of CD44 have been attributed to the generation of a functionally active hyaluronan-binding phenotype. Orchitis was induced in Sprague–Dawley adult rats by active immunization with an emulsion of testicular homogenate and complete Freund’s adjuvant using Bordetella pertussis as co-adjuvant. Control rats (C) injected with saline and adjuvants and normal (N) untreated rats were also studied. CD44 expression was analyzed by flow cytometry in peripheral blood mononuclear cells (PBMC) and lymph node cells isolated from rats at different times after the first immunization. We observed an increase in the mean fluorescence intensity of both samples in the C and experimental (E) groups only after the immunization period. A significant decrease in percentage of CD44 + PBMC and in mean fluorescence intensity was observed in rats with orchitis compared with the C group. By in vitro hyaluronic acid-binding assay we demonstrated that the percentage of PBMC adhesion was higher in the E group compared with the C and N groups. By immunohistochemistry, we observed a significant increase in the number of CD44 + cells in the testicular interstitium of rats with severe orchitis compared with the N and C groups. These results suggested that the CD44 molecule is involved in the homing of lymphomonocytes into the testes of rats with autoimmune orchitis.

scholarly journals Correlation between inhibin secretion and damage of seminiferous tubules in a model of experimental autoimmune orchitis

2001 ◽  
Vol 170 (1) ◽  
pp. 113-120 ◽  
Author(s):  
MO Suescun ◽  
MO Suescun ◽  
L Lustig ◽  
RS Calandra ◽  
RS Calandra ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Inverse Correlation ◽  
Inhibin B ◽  
Alpha Subunit ◽  
Germinal Epithelium ◽  
Seminiferous Tubules ◽  
Positive Staining ◽  
Testis Weight ◽  
Autoimmune Orchitis ◽  
Experimental Autoimmune

The aim of the present study was to evaluate inhibin secretion in rats with autoimmune orchitis. As we have previously described, experimental autoimmune orchitis (EAO) induced in rats by active immunization with testis homogenate and adjuvants is characterized by an interstitial mononuclear cell infiltrate and sloughing of the germinal epithelium. At 120 days after the first immunization 60% of the rats exhibited a severe orchitis with large areas of aspermatogenic seminiferous tubules in which only spermatogonia and Sertoli cells with cytoplasmic vacuolization remained attached to the tubular wall. None of the untreated (N) or control (C) rats revealed pathological alterations. Sixty percent decrease in testis weight was observed in rats with EAO compared with N or C groups. A 3-fold increase in serum FSH levels was observed in rats with EAO compared with N or C groups (19.8+/-3.7 vs 5.6+/-0.3 and 5.9+/-0.1 ng/ml respectively). A significant decrease in inhibin B levels was observed in rats with EAO when compared with N or C groups (40+/-4.6 vs 207+/-38.8 and 221.4+/-28.6 pg/ml respectively). An inverse correlation between inhibin B and FSH serum levels and a direct correlation between inhibin B and testis weight were found. Strong expression of the inhibin alpha-subunit in Sertoli cells of untreated and control rats was observed; this subunit was undetectable or poorly detectable in rats with orchitis. Positive staining for the inhibin alpha-subunit was also observed in Leydig cells of all groups studied. In conclusion, using a model of autoimmune orchitis our results show that circulating inhibin B levels and inhibin alpha-subunit expression in Sertoli cell cytoplasm closely correlate with the degree of damage of the germinal epithelium.

1509: Adeno-Associated Virus-Mediated Human IL-10 Gene Transfer Suppresses the Development of Experimental Autoimmune Orchitis

2005 ◽  
Vol 173 (4S) ◽  
pp. 409-409
Author(s):  
Masami Watanabe ◽  
Atsushi Nagai ◽  
Norihiro Kusumi ◽  
Yasutomo Nasu ◽  
Hiromi Kumon ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Adeno Associated Virus ◽  
Autoimmune Orchitis ◽  
Experimental Autoimmune

scholarly journals Histopathological analysis of the reproductive system of male dogs experimentally infected with Toxoplasma gondii

2009 ◽  
Vol 39 (7) ◽  
pp. 2123-2127 ◽  
Author(s):  
Tiago Pereira Arantes ◽  
Welber Daniel Zanetti Lopes ◽  
Roberta Machado Ferreira ◽  
Juliana de Souza Pinto Pieroni ◽  
Vanessa Marigo Rocha Pinto ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Reproductive System ◽  
Interstitial Fibrosis ◽  
Optical Microscope ◽  
Seminiferous Tubules ◽  
Histopathological Analysis ◽  
Hydropic Degeneration ◽  
Toxoplasmic Infection ◽  
Toxoplasma Gondii Infection ◽  
Histopathological Results

The present research aimed to describe possible histopathological alterations in the reproductive system (testicles and epididymis) of male dogs experimentally infected with Toxoplasma gondii. Canines (n=10) serologically negative for T. gondii were selected and distributed into three experimental groups: GI, 3 inoculated with 2.0 x 10(5)P strain oocysts; GII, 3 infected with 1.0 x 10(6)RH strain tachyzoites; and GIII, 4 control dogs. Antibody research (IFAT) against T. gondii was realized. Toxoplasma gondii infection was confirmed by seroconversion of the 6 males infected with tachyzoites and oocysts from postinoculation day (PID) 7 and 14, respectively. At PID 70, all dogs were submitted to orchiectomy and testicle and epididymis samples were collected and histologically processed for examination under optical microscope. The following alterations were diagnosed: mild and moderate mononuclear inflammatory infiltrate in the epididymis, moderate cellular edema, hydropic degeneration and moderate interstitial fibrosis in seminiferous tubules. The histopathological results in the present research, isolation of T. gondii in testicle and epididymis fragments by immunohistochemistry and results from the literature by other authors in different tissues, all infer that the alterations observed in dogs infected with T. gondii are suggestive of toxoplasmic infection.

scholarly journals Signaling Pathways Involved in Diabetic Renal Fibrosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuqing Zhang ◽  
De Jin ◽  
Xiaomin Kang ◽  
Rongrong Zhou ◽  
Yuting Sun ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Renal Fibrosis ◽  
Diabetic Kidney Disease ◽  
Interstitial Fibrosis ◽  
New Drugs ◽  
Therapeutic Effects ◽  
Renal Interstitial Fibrosis ◽  
Notch Pathways ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD), as the most common complication of diabetes mellitus (DM), is the major cause of end-stage renal disease (ESRD). Renal interstitial fibrosis is a crucial metabolic change in the late stage of DKD, which is always considered to be complex and irreversible. In this review, we discuss the pathological mechanisms of diabetic renal fibrosis and discussed some signaling pathways that are closely related to it, such as the TGF-β, MAPK, Wnt/β-catenin, PI3K/Akt, JAK/STAT, and Notch pathways. The cross-talks among these pathways were then discussed to elucidate the complicated cascade behind the tubulointerstitial fibrosis. Finally, we summarized the new drugs with potential therapeutic effects on renal fibrosis and listed related clinical trials. The purpose of this review is to elucidate the mechanisms and related pathways of renal fibrosis in DKD and to provide novel therapeutic intervention insights for clinical research to delay the progression of renal fibrosis.

Comparative analysis of expression profiles of chemokines, chemokine receptors, and components of signaling pathways mediated by chemokines in eight cell types during rat liver regeneration

Genome ◽  
2010 ◽  
Vol 53 (8) ◽  
pp. 608-618 ◽  
Author(s):  
Xiaoguang Chen ◽  
Cunshuan Xu ◽  
Fuchun Zhang ◽  
Ji Ma
Keyword(s):  
Liver Regeneration ◽  
Signaling Pathways ◽  
Expression Profiles ◽  
Gradient Centrifugation ◽  
Cell Types ◽  
Cellular Level ◽  
Pcr Analysis ◽  
Immunomagnetic Bead ◽  
Percoll Density Gradient Centrifugation ◽  
Chemokine Signaling

It has been documented that chemokines can positively regulate liver regeneration at the tissue level after partial hepatectomy. However, the precise mechanism of the effects of chemokines on regeneration at the cellular level remains poorly defined. In this study, 8 cell types from rat regenerating liver at 8 recovery time points after 2/3 hepatectomy were isolated and purified using Percoll density gradient centrifugation and immunomagnetic bead methods. The expression profiles of each cell type were monitored using a microarray. RT-PCR analysis was performed to validate the reliability of the microarray results. The results showed that, on the whole, the expression profiles of chemokine and receptor genes varied among different cell types; most genes involved in chemokine signaling pathways showed an increase in expression across the 8 liver cell types during liver regeneration. The implication of these genes in regeneration was analyzed by bioinformatics and systems biology methods. According to the microarray results and gene synergy, activation of chemokine signaling pathways at 24 h in biliary epithelial cells and at 2–12 h in dendritic cells may be triggered by CCL2–CCR2 and CCL7–CCR3, respectively; activation of Plc/Pkc and Pi3k/Akt pathways at 2–12 h in sinusoidal endothelial cells might be caused by CCL7–CCR1; and activation of the Src/Ptk, Src/Vav, and Plc/Pkc pathways at the priming stage may be related to the inductive effect of CCL7. These data suggest the potential relevance of the pro-inflammatory chemokines for liver regeneration at the cellular level.

Rapid generation of Hybrid Biochemical/Mechanical Cues in Heterogeneous Droplets for High-Throughput Screening of Cellular Response

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Xing Zhao ◽  
Gaozhi Ou ◽  
Mengcheng Lei ◽  
Yang Zhang ◽  
Lina Li ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
High Throughput ◽  
High Throughput Screening ◽  
Cellular Response ◽  
Wide Range ◽  
Rapid Generation ◽  
P Cells

Cells in native microenvironment are subjected to varying combinations of biochemical cues and mechanical cues in a wide range. Despite many signaling pathways have been found to be responsive for...

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