Ethanol-related transcriptomic changes in mouse testes
Ontology highlight
ABSTRACT:
SUBMITTER: Han G
PROVIDER: S-EPMC11337739 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The pig is an important model for studying human diseases and is also a significant livestock species, yet its testicular development remains underexplored. Here, we employ single-cell RNA sequencing to characterize the transcriptomic landscapes across multiple developmental stages of Bama pig testes from fetal stage through infancy, puberty to adulthood, and made comparisons with those of humans and mice. We reveal an exceptionally early onset of porcine meiosis shortly after birth, and identify a distinct subtype of porcine spermatogonia resembling transcriptome state 0 spermatogonial stem cells identified in humans, which were previously thought to be primate specific. We also discover the persistent presence of proliferating progenitors for myoid cells in postnatal testes. The regulatory roles of Leydig cell steroidogenesis and estrogen synthesis in supporting cell lineages are also explored, including the potential impact of estrogen on Sertoli cell maturation and spermatogenesis. Overall, this study offers valuable insights into porcine testicular development, paving the way for future research in reproductive biology, advancements in agricultural breeding, and potential applications in translational medicine.
| S-EPMC11550399 | biostudies-literature
Project description:Glomerular podocytes undergo structural and functional changes with advanced age, that increase susceptibility of aging kidneys to worse outcomes following superimposed glomerular diseases. To delineate transcriptional changes in podocytes in aged mice, RNA-seq was performed on isolated populations of reporter-labeled (tdTomato) podocytes from multiple young (two to three months) and advanced aged mice (22 to 24 months, equivalent to 70 plus year old humans). Of the 2,494 differentially expressed genes, 1,219 were higher and 1,275 were lower in aged podocytes. Pathway enrichment showed that major biological processes increased in aged podocytes included immune responses, non-coding RNA metabolism, gene silencing and MAP kinase signaling. Conversely, aged podocytes showed downregulation of developmental, morphogenesis and metabolic processes. Canonical podocyte marker gene expression decreased in aged podocytes, with increases in apoptotic and senescence genes providing a mechanism for the progressive loss of podocytes seen with aging. In addition, we revealed aberrations in the podocyte autocrine signaling network, identified the top transcription factors perturbed in aged podocytes, and uncovered candidate gene modulations that might promote healthy aging in podocytes. The transcriptional signature of aging is distinct from other kidney diseases. Thus, our study provides insights into biomarker discovery and molecular targeting of the aging process itself within podocytes.
| S-EPMC7606654 | biostudies-literature
Project description:Substantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease (PD). Until now, molecular mechanisms behind SNpc aging have not been fully investigated using high throughput techniques. Here, we show early signs of aging in SNpc, which are more evident than in ventral tegmental area (VTA), a region adjacent to SNpc but less affected in PD. Aging-associated early changes in transcriptome were investigated comparing late middle-aged (18 months old) to young (2 months old) mice in both SNpc and VTA. A meta-analysis of published microarray studies allowed us to generate a common "transcriptional signature" of the aged (? 24 months old) mouse brain. SNpc of late-middle aged mice shared characteristics with the transcriptional signature, suggesting an accelerated aging in SNpc. Age-dependent changes in gene expression specific to SNpc were also observed, which were related to neuronal functions and inflammation. Future studies could greatly help determine the contribution of these changes to SNpc aging. These data help understand the processes underlying SNpc aging and their potential contribution to age-related disorders like PD.
| S-EPMC3640071 | biostudies-literature
Project description:BackgroundThe benefits of physical activity for the overall well-being of elderly individuals are well-established, the precise mechanisms through which exercise improves pathological changes in the aging lens have yet to be fully understood.Methods3-month-old C57BL/6J mice comprised young sedentary (YS) group, while aging mice (18-month-old) were divided into aging sedentary (AS) group and aging exercising (AE) group. Mice in AE groups underwent sequential stages of swimming exercise. H&E staining was employed to observe alterations in lens morphology. RNA-seq analysis was utilized to examine transcriptomic changes. Furthermore, qPCR and immunohistochemistry were employed for validation of the results.ResultsAE group showed alleviation of histopathological aging changes in AS group. By GSEA analysis of the transcriptomic changes, swimming exercise significantly downregulated approximately half of the pathways that underwent alterations upon aging, where notable improvements were 'calcium signaling pathway', 'neuroactive ligand receptor interaction' and 'cell adhesion molecules'. Furthermore, we revealed a total of 92 differentially expressed genes between the YS and AS groups, of which 10 genes were observed to be mitigated by swimming exercise. The result of qPCR was in consistent with the transcriptome data. We conducted immunohistochemical analysis on Ciart, which was of particular interest due to its dual association as a common aging gene and its significant responsiveness to exercise. The Protein-protein Interaction network of Ciart showed the involvement of the regulation of Rorb and Sptbn5 during the process.ConclusionThe known benefits of exercise could extend to the aging lens and support further investigation into the specific roles of Ciart-related pathways in aging lens.
| S-EPMC10913554 | biostudies-literature
Project description:Anastasis is a cell recovery mechanism that rescues dying cells from the brink of death. Reversal of apoptosis is the first example of anastasis. Here, we describe a comprehensive dataset containing time-course mRNA expression profiles for reversal of ethanol-induced apoptosis in mouse primary liver cells in νitro. This transcriptome dataset includes the conditions of the untreated cells, cells undergoing apoptosis triggered by incubating with cell death inducer of 4.5% ethanol for 5 hours, and apoptosis reversal of ethanol-induced cells at the early (3rd hour), middle (6th hour), and late (24th, 48th hour) stages after being washed with and incubated in fresh cell culture medium. By comparing this dataset with the transcriptomic profiles of other anastasis models generated with different combinations of cell types and cell death inducers, investigators can identify the key regulators governing reversal of apoptosis and other reversible cell death processes. Therefore, reusing or reanalysing this dataset will facilitate the future studies on the physiological, pathological, and therapeutic implications of anastasis.
| S-EPMC9293995 | biostudies-literature
Project description:The phosphatidylinositol 3' kinase (PI3K)-related kinase ATR is crucial for mammalian meiosis. ATR promotes meiotic progression by coordinating key events in DNA repair, meiotic sex chromosome inactivation (MSCI), and checkpoint-dependent quality control during meiotic prophase I. Despite its central roles in meiosis, the ATR-dependent meiotic signaling network remains largely unknown. Here, we used phosphoproteomics to define ATR signaling events in testes from mice following chemical and genetic ablation of ATR signaling. Quantitative analysis of phosphoproteomes obtained after germ cell-specific genetic ablation of the ATR activating 9-1-1 complex or treatment with ATR inhibitor identified over 14,000 phosphorylation sites from testes samples, of which 401 phosphorylation sites were found to be dependent on both the 9-1-1 complex and ATR. Our analyses identified ATR-dependent phosphorylation events in crucial DNA damage signaling and DNA repair proteins including TOPBP1, SMC3, MDC1, RAD50, and SLX4. Importantly, we identified ATR and RAD1-dependent phosphorylation events in proteins involved in mRNA regulatory processes, including SETX and RANBP3, whose localization to the sex body was lost upon ATR inhibition. In addition to identifying the expected ATR-targeted S/T-Q motif, we identified enrichment of an S/T-P-X-K motif in the set of ATR-dependent events, suggesting that ATR promotes signaling via proline-directed kinase(s) during meiosis. Indeed, we found that ATR signaling is important for the proper localization of CDK2 in spermatocytes. Overall, our analysis establishes a map of ATR signaling in mouse testes and highlights potential meiotic-specific actions of ATR during prophase I progression.
| S-EPMC8824463 | biostudies-literature
Project description:We have shown that zebrafish (Danio rerio) are an excellent model for evaluating the link between early life stage exposure to environmental chemicals and disease in adulthood and subsequent unexposed generations. Previously, we used this model to identify transgenerational effects of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]) on skeletal development, sex ratio, and reproductive capacity. Transgenerational inheritance of TCDD toxicity, notably decreased reproductive capacity, appears to be mediated through the male germ line. Thus, we examine testicular tissue for structural and gene expression changes using histology, microarray, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Histological analysis revealed decreased spermatozoa with concurrent increase in spermatogonia, and decreased germinal epithelium thickness in TCDD-exposed males compared with controls. We also identified altered expression of genes associated with testis development, steroidogenesis, spermatogenesis, hormone metabolism, and xenobiotic response. Altered genes are in pathways involving lipid metabolism, molecular transport, small molecule biochemistry, cell morphology, and metabolism of vitamins and minerals. These data will inform future investigations to elucidate the mechanism of adult-onset and transgenerational infertility due to TCDD exposure in zebrafish.
| S-EPMC5035372 | biostudies-literature
Project description:Spermatogenesis is an efficient and complex system of continuous cell differentiation. Previous studies investigating the transcriptomes of different cell populations in the testis relied either on sorting cells, cell depletion, or juvenile animals where not all stages of spermatogenesis have been completed. We present single-cell RNA sequencing (scRNA-Seq) data of 2,500 cells from the testes of two 8-week-old C57Bl/6J mice. Our dataset includes all spermatogenic stages from preleptotene to condensing spermatids as well as individual spermatogonia, Sertoli and Leydig cells. The data capture the full continuity of the meiotic and postmeiotic stages of spermatogenesis, and is thus ideally suited for marker discovery, network inference and similar analyses for which temporal ordering of differentiation processes can be exploited. Furthermore, it can serve as a reference for future studies involving single-cell RNA-Seq in mice where spermatogenesis is perturbed.
| S-EPMC6132189 | biostudies-literature
Project description:Alcohol use disorder (AUD) is a devastating psychiatric disorder that has significant wide-reaching effects on individuals and society. Selectively bred mouse lines are an effective means of exploring the genetic and neuronal mechanisms underlying AUD and such studies are translationally important for identifying treatment options. Here, we report on behavioral characterization of two replicate lines of mice that drink to intoxication, the High Drinking in the Dark (HDID)-1 and -2 mice, which have been selectively bred (20+ generations) for the primary phenotype of reaching high blood alcohol levels (BALs) during the drinking in the dark (DID) task, a binge-like drinking assay. Along with their genetically heterogenous progenitor line, Hs/Npt, we tested these mice on: DID and drinking in the light (DIL); temporal drinking patterns; ethanol sensitivity, through loss of righting reflex (LORR); and operant self-administration, including fixed ratio (FR1), fixed ratio 3:1 (FR3), extinction/reinstatement, and progressive ratio (PR). All mice consumed more ethanol during the dark than the light and both HDID lines consumed more ethanol than Hs/Npt during DIL and DID. In the dark, we found that the HDID lines achieved high blood alcohol levels early into a drinking session, suggesting that they exhibit front loading like drinking behavior in the absence of the chronicity usually required for such behavior. Surprisingly, HDID-1 (female and male) and HDID-2 (male) mice were more sensitive to the intoxicating effects of ethanol during the dark (as determined by LORR), while Hs/Npt (female and male) and HDID-2 (female) mice appeared less sensitive. We observed lower HDID-1 ethanol intake compared to either HDID-2 or Hs/Npt during operant ethanol self-administration. There were no genotype differences for either progressive ratio responding, or cue-induced ethanol reinstatement, though the latter is complicated by a lack of extinguished responding behavior. Taken together, these findings suggest that genes affecting one AUD-related behavior do not necessarily affect other AUD-related behaviors. Moreover, these findings highlight that alcohol-related behaviors can also differ between lines selectively bred for the same phenotype, and even between sexes within those same line.
| S-EPMC7915226 | biostudies-literature
Project description:Aging of the retinal pigment epithelium (RPE) leads to a gradual decline in RPE homeostasis over time, significantly impacting retinal health. Understanding the mechanisms underlying RPE aging is crucial for elucidating the background in which many age-related retinal pathologies develop. In this study, we compared the transcriptomes of young and aged mouse RPE and found a marked upregulation of immunogenic and proinflammatory genes in aging RPE. Additionally, aging RPE exhibited dysregulation of pathways associated with visual perception and extracellular matrix production. Research on aging in post-natal quiescent RPE is hindered by the absence of relevant in vitro models. We evaluated an in vitro model of chronologically aged primary human RPE to address this gap, which displayed gene expression patterns comparable to native-aged RPE. Profiling this in vitro aging model highlighted its potential utility in investigating cellular and molecular mechanisms of RPE aging and in preliminary testing of therapeutic compounds. Overall, our findings suggest chronological aging of RPE leads to the acquisition of a proinflammatory phenotype, impacting RPE function and serving as a significant factor in the development of age-related retinal pathologies.
2024-05-10 | GSE263427 | GEO