Single-cell Transcriptome Atlas of Testis Aging
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE215754 | GEO | 2022/10/17
REPOSITORIES: GEO
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Project description:As a unique population of testicular mesenchymal stromal cells, stem Leydig cells (SLCs) have shown great promise in the treatment of male hypogonadism. The therapeutic functions of MSCs are largely determined by their reciprocal regulation by immune responses. However, the immunoregulatory properties of SLCs have not been fully studied. Here, we found that transplanted SLCs restored testicular immunological homeostasis via damage signal-triggered transient receptor potential cation channel subfamily member 7 (TRPM7)-mediated mitochondrial transfer to macrophages. Specifically, the results showed that SLCs transplantation restored male fertility and testosterone production in an ischemia‒reperfusion injury-induced acute inflammation model. This was achieved mainly via a mechanism involving the prevention of inflammatory cascades but not the differentiation to Leydig cells (LCs), the main testosterone-producing cells. Furthermore, we identified that ROS released from activated macrophages, which are the primary testicular immunocytes, induced nanotube-mediated mitochondrial transfer from SLCs to macrophages via TRPM7. Notably, TRPM7 knockdown by interfering RNA in transplanted SLCs compromised the therapeutic outcomes in both testicular ischemia‒reperfusion and testicular aging mouse models. Collectively, SLC rescued testicular damage in testicular ischemia‒reperfusion mouse models, and the damage signal activated TRPM7 signaling and induced mitochondrial transfer from SLCs to macrophages, playing important roles in the repair of SLCs. These findings provide insight into the clinical translation of SLCs and suggest that strategies targeting mitochondrial transfer may be effective treatments for patients with male hypogonadism related to immune disorders.
2024-02-01 | GSE254881 | GEO
Project description:Aging human males display reduced reproductive health, however testis aging is poorly understood at the molecular and genomic level. Here, we utilized single-cell RNA-seq to profile over 44,000 cells from both young and older men (>60 years old) – and examined age-related changes in germline development and in the somatic niche. Interestingly, age-related changes in spermatogonial stem cells appeared modest, whereas age-related dysregulation of spermatogenesis and the somatic niche ranged from moderate to severe. Altered pathways included signaling and inflammation in multiple cell types, metabolic signaling in Sertoli cells, hedgehog signaling and testosterone production in Leydig cells, cell death and growth in testicular peritubular cells, and possible developmental regression in both Leydig and peritubular cells. Remarkably, the extent of dysregulation correlated with body mass index in older, but not younger men. Taken together, we reveal candidate molecular mechanisms underlying the complex testicular changes conferred by aging, and their exacerbation by concurrent chronic conditions such as obesity.
2022-05-05 | GSE182786 | GEO
Project description:In humans, the most common sex chromosomal disorder is Klinefelter syndrome (KS), caused by the presence of one or more extra X-chromosomes. The KS patients display a diverse adult phenotype with increased height, gynaecomastia, and hypergonadotropic hypogonadism as the most common symptoms. Men with KS are almost always infertile due to testicular degeneration, which accelerates during puberty. Very few studies investigated when the germ cell loss begins and whether it is caused by dysgenetic fetal development of the testes. We investigated a series of fetal KS testis tissue samples and found a marked reduction in MAGE-A4-positive pre-spermatogonia in the developing KS gonads compared to controls, indicating a failure of the gonocytes to differentiate into pre-spermatogonia. Transcriptome analysis by RNA sequencing of formalin-fixed and paraffin embedded gonads originating from 4 fetal KS samples and 5 age- and cellularity-matched controls revealed 211 differentially expressed transcripts in the fetal KS testis. We found a significant enrichment of upregulated X-chromosomal transcripts and validated the expression of the pseudoautosomal region 1 (PAR1) gene, AKAP17A. Moreover, we found enrichment of long non-coding RNAs in the KS testes (e.g. LINC01569 and RP11-485F13.1). In conclusion, our data indicates that the testicular phenotype observed among adult men with KS is initiated already in fetal life by failure of the gonocyte differentiation into pre-spermatogonia, which could be due to aberrant expression of long non-coding RNAs.
2018-08-28 | GSE103613 | GEO
Project description:In humans, the most common sex chromosomal disorder is Klinefelter syndrome (KS), caused by the presence of one or more extra X-chromosomes. The KS patients display a diverse adult phenotype with increased height, gynaecomastia, and hypergonadotropic hypogonadism as the most common symptoms. Men with KS are almost always infertile due to testicular degeneration, which accelerates during puberty. Very few studies investigated the global gene expression analysis of adult KS testes and, more importantly, which cell types the differentially expressed transcripts originate from. Transcriptome analysis by RNA sequencing of fixed and paraffin embedded testes originating from 3 adult KS samples and 3 adult cellularity-matched controls revealed 236 differentially expressed transcripts in the adult KS testis. To examine the cellular origin of the differentially expressed transcripts, transcriptome profiling was also carried out on 4 testes with Sertoli Cell-Only and 4 testes with full spermatogenesis. Also, pre-pubertal KS and controls were RNA-sequenced.
2018-05-30 | GSE103905 | GEO
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Project description:The overall objective of this proposal is to map the temporal and spatial dynamics of gene expression in the fetal mouse testis at key developmental timepoints. Urogenital tract malformations are the most common birth defects in males and their incidence together with other male reproductive health concerns such as reduced fertility and testicular cancer are reportedly on the rise in the human population. To better understand the impact of genetic factors and environmental influences on testicular development, it is important to first understand normal gene expression patterns and signaling cascades within the fetal testis during development. The goal of this study is to identify cell-specific genes that can be used as biomarkers for key differentiation events.
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Project description:An excess in thyroid hormone during rodent neonatal life causes abnormal prolifration and maturation of testicular cells, leading to reduced testis size and impairments in steroidogenesis, Sertoli cell function, spermatogenesis and fertility. The high expression of type 3 deiodinase in the neonatal testis protects this tissue from premature exposure to thyroid hormones, since this gene (Dio3) function is to degrade thyroid hormones. DIO3-deficient mice (Dio3KO) exhibit a marked reduction in Sertoli cell proliferation and testis size, abnormalities in the reproductive axis and impaired fertility (Martinez et al. 2016, Endocrinology157:1276). To identify genes that are untimely regulated by thyroid hormone in the developing testes, we have performed RNAseq in testis total RNA from wild type and DIO3KO mouse neonates.
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Project description:1α,25(OH)2VD3 is the most active form of VD3 in animals and it plays an important role in regulating mineral metabolism but also reproduction and immunity. Testes are the main reproductive organs of male mammals. In order to study the effect of 1α,25(OH)2VD3 on early testicular development, 140 weaned 21-day old piglets were selected. The piglets were randomly divided into four groups and were fed a commercial diet supplemented with 0, 1, 2 and 4 μg.kg-1 of 1α,25(OH)2VD3, provided as 1α,25(OH)2VD3-glycosides, 60 days after the start of the experiment, at piglet age 82 days, testes were harvested. The morphology and histology of early testicular development were assessed. In addition, the proteomic TMT/iTRAQ labeling technique was used to analyze the protein profile of the testes in each group. Western blotting was used to verify the target of differentially abundant proteins (DAPs). The results showed that of the identified 132715 peptides, 122755 were specific peptides. 7852 proteins, of which 6573 proteins contain quantitative information. Screening for DAPs was focused on proteins closely related to the regulation of the testicular development such as steroid hormone synthesis, steroid biosynthesis, peroxisome and fatty acid metabolism pathways. These results also indicate that 1α,25(OH)2VD3 is involved in the regulation of early testicular development in piglets. At the same time, these findings provide valuable information for the proteins involved in the regulation of testicular development, and help to better understand the mechanisms of 1α,25(OH)2VD3 in regulating the development of piglets’ testes. Significance: The early development of the testes of breeding boars is closely related to their lifetime fertility. Our research identifies potential signaling pathways and differentially abundant proteins associated with testicular development. These findings indicate that plants containing 1α,25(OH)2VD3-glycosides used as a nutritional ingredient may help early testicular development in breeding boars and reveal the regulatory mechanism of 1α,25(OH)2VD3 on testicular development.
2021-09-09 | PXD022090 | Pride
Project description:Identification of gene expression patterns that correlate with distinct stages of male germ cell development using biopsies from men with highly defined and homogenous testicular pathologies based on the Johnsen score procedure. The Johnsen score procedure is a classical histopathological scoring procedure that classifies the germ cell composition from different stages of spermatogenic impairment.
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Project description:The aim of this investigation was to develop a global view of muscle transcriptional differences between older men and women and with aging for each sex. Muscle biopsies were obtained from the biceps brachii of young (age 19~28yrs) and older (age 65~76 yrs) men (7 young, 4 older) and women (7 young, 4 older). Total RNA was extracted and gene expression profiling was performed using the Affymetrix Human Genome U133 Plus 2 chip.
2013-02-28 | E-GEOD-38718 | biostudies-arrayexpress