scholarly journals Correlation between the aberrant human testicular germ-cell gene expression and disruption of spermatogenesis leading to male infertility

2018 ◽  
Author(s):  
Arka Baksi ◽  
Ruchi Jain ◽  
Ravi Manjithaya ◽  
S S Vasan ◽  
Paturu Kondaiah ◽  
...  

AbstractSpermatogenesis is characterized by sequential gene-expression at precise stages in progression of differentiation of the germ cells. Any alteration in expression of the critical genes is responsible for arrest of spermatogenesis associated with infertility. Inspite of advances the differential gene expression accompanying spermatogenesis, the corresponding regulatory mechanisms and their correlation to human infertility have not been clearly established. This study aims to identify the gene expression pattern of the human testicular germ cells from the patients either with obstructive azoospermia with complete intra-testicular spermatogenesis or non-obstructive azoospermia with spermatogenesis arrested at different stages and correlate the same to infertility. The testicular transcriptomes of 3 OA and 8 NOA patients and pooled testicular RNA (commercial source) were analyzed for their differential gene expression to identify potential regulators of spermatogenesis and the results were further validated in all of the 44 patients clinically diagnosed with azoospermia undergoing sperm retrieval surgery over the study period and 4 control samples included in this study. Analyses of the differential transcriptome led to identification of genes enriched in a specific testicular cell type and subsequently, several regulators of the diploid-double-diploid-haploid transitions in the human spermatogenesis were identified. Perturbations in the expression of these genes were identified as the potential causes of the spermatogenic arrest seen in azoospermia and thus the potential mediators of human male infertility. Another interesting observation was the increased autophagy in the testes of patients with non-obstructive azoospermia. The present study suggests that the regulation of the diploid-double-diploid-haploid transition is multigenic with the tandem alteration of several genes resulting in infertility. In conclusion, this study identified some of the genetic regulators controlling spermatogenesis using comparative transcriptome analyses of testicular tissues from azoospremic individuals and showed how alterations in several genes results in disruption of spermatogenesis and subsequent infertility. This study also provides interesting insights into the gene expression patterns of the Indian population that were not available earlier.

2020 ◽  
Author(s):  
Mei Luo ◽  
Zhangyong Dong ◽  
Yongxin Shu ◽  
Mobing Chen

Abstract Background: Trichoderma koningiopsis strain Tk1 shows good biocontrol potential. However, its biocontrol function may differ under different conditions. The objective of this study is to elucidate the biological and transcriptome differences of T. koningiopsis Tk1 under different media. Results: In this study, the mycelium weight and sporulation of T. koningiopsis Tk1 was found to differ in various media. Further, the Tk1 strain inhibited the growth of the pathogen Fusarium oxysporum in the three media tested. Fries3, PD, and PS were collected for RNA sequencing of Tk1 mycelia to identify the genes that are differentially expressed genes (DEGs) between Tk1 grown on different media. De novo transcriptome assembly resulted in identification of 14,208 unigenes. The differential gene expression pattern was more similar between the Fries3 and PS samples, whereas PD samples showed a different expression pattern. The DEGs were enriched in some metabolic and biosynthetic pathways. Additional analysis of the DEGs identified a set of carbohydrate-active enzymes that are upregulated or downregulated under different conditions.Conclusions: These results indicate that the Tk1 strain cultured in Fires3 and PS mediums can produce specific metabolic and carbohydrate-active enzymes to enhance their antimicrobial effect, providing a foundation for the subsequent mining of specific genes.


2021 ◽  
Vol 22 (15) ◽  
pp. 8205
Author(s):  
Julie Rae ◽  
Jason Hackney ◽  
Kevin Huang ◽  
Mary Keir ◽  
Ann Herman

Interleukin-22 (IL-22) plays a role in epithelial barrier function and repair, and may provide benefits in conditions like inflammatory bowel disease. However, limited human data are available to assess the clinical effect of IL-22 administration. This study used a human intestinal cell line to identify an IL-22-dependent gene signature that could serve as a pharmacodynamic biomarker for IL-22 therapy. The response to IL-22Fc (UTTR1147A, an Fc-stabilized version of IL-22) was assessed in HT-29 cells by microarray, and the selected responsive genes were confirmed by qPCR. HT-29 cells demonstrated dose-dependent increases in STAT3 phosphorylation and multiple gene expression changes in response to UTTR1147A. Genes were selected that were upregulated by UTTR1147A, but to a lesser extent by IL-6, which also signals via STAT3. IL-1R1 was highly upregulated by UTTR1147A, and differential gene expression patterns were observed in response to IL-22Fc in the presence of IL-1β. An IL-22-dependent gene signature was identified that could serve as a pharmacodynamic biomarker in intestinal biopsies to support the clinical development of an IL-22 therapeutic. The differential gene expression pattern in the presence of IL-1β suggests that an inflammatory cytokine milieu in the disease setting could influence the clinical responses to IL-22.


2019 ◽  
Vol 20 (23) ◽  
pp. 6098 ◽  
Author(s):  
Amarinder Singh Thind ◽  
Kumar Parijat Tripathi ◽  
Mario Rosario Guarracino

The comparison of high throughput gene expression datasets obtained from different experimental conditions is a challenging task. It provides an opportunity to explore the cellular response to various biological events such as disease, environmental conditions, and drugs. There is a need for tools that allow the integration and analysis of such data. We developed the “RankerGUI pipeline”, a user-friendly web application for the biological community. It allows users to use various rank based statistical approaches for the comparison of full differential gene expression profiles between the same or different biological states obtained from different sources. The pipeline modules are an integration of various open-source packages, a few of which are modified for extended functionality. The main modules include rank rank hypergeometric overlap, enriched rank rank hypergeometric overlap and distance calculations. Additionally, preprocessing steps such as merging differential expression profiles of multiple independent studies can be added before running the main modules. Output plots show the strength, pattern, and trends among complete differential expression profiles. In this paper, we describe the various modules and functionalities of the developed pipeline. We also present a case study that demonstrates how the pipeline can be used for the comparison of differential expression profiles obtained from multiple platforms’ data of the Gene Expression Omnibus. Using these comparisons, we investigate gene expression patterns in kidney and lung cancers.


2002 ◽  
Vol 278 (9) ◽  
pp. 7540-7552 ◽  
Author(s):  
Swapnil R. Chhabra ◽  
Keith R. Shockley ◽  
Shannon B. Conners ◽  
Kevin L. Scott ◽  
Russell D. Wolfinger ◽  
...  

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