Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Uchl1 maintains energy and metabolic homeostatic balance during spermatogenesis

ABSTRACT: In mammals, spermatogenesis plays a critical role in upholding the genetic stability of the male germline; however, disruptions such as viral and bacterial infections, toxic damage, genetic mutations, or deletions can disturb the delicate equilibrium of the testicular microenvironment, ultimately resulting in impaired spermatogenesis and male infertility. One key protein involved in this process is UCHL1, which possesses deubiquitinating enzyme, multiple ligases, and hydrolase activities. In addition to its roles in maintaining neuronal activity and memory function in the brain, UCHL1 is also implicated in spermatogenesis. Nevertheless, the precise mechanism by which it sustains metabolic homeostasis during spermatogenesis remains unclear. To investigate this, we generated Uchl1_KO mice and subjected their testes to snRNA-seq and metabolomics sequencing. Our analysis revealed that Uchl1_KO mice exhibited abnormal spermatogenesis, decreased testicular OXHPOS levels, and disrupted ADIPONECTIN signaling, concomitant with heightened inflammatory signaling and disturbances in lipid metabolism and energy homeostasis in the testes. These findings suggest that Uchl1 plays a crucial role in spermatogenesis by modulating energy and metabolic pathways within the testes to maintain orderly spermatogenesis. This study contributes to the understanding of the energy and metabolic balance required for successful male spermatogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE267378 | GEO | 2025/05/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Uchl1 maintains energy and metabolic homeostatic balance during spermatogenesis

Project description:Uchl1 maintains energy and metabolic homeostatic balance during spermatogenesis

| PRJNA1111379 | ENA

Metabolic reprogramming in astrocytes prevents neuronal death through a UCHL1/PFKFB3/H4K8la positive feedback loop

Project description:Astrocytic metabolic reprogramming is an adaptation of metabolic patterns to meet increased energy demands, although the role after spinal cord injury (SCI) remains unclear. Analysis of single-cell RNA sequencing (scRNA-seq) data identified an increase in astrocytic glycolysis, while PFKFB3, a key regulator of glycolytic flux, was significantly upregulated following SCI. Loss of PFKFB3 in astrocytes prohibited neuronal energy supply and enhanced neuronal ferroptosis in vitro and inhibited astrogliosis, expanded neuroinflammation, exacerbated neuronal loss, and hindered functional recovery in vivo after SCI. Mechanistically, deubiquitinase UCHL1 plays a crucial role in stabilizing and enhancing PFKFB3 expression by cleaving K48-linked ubiquitin chains. Genetic deletion of Uchl1 inhibited locomotor recovery after SCI by suppression of PFKFB3-induced glycolytic reprogramming in astrocytes. Furthermore, the UCHL1/PFKFB3 axis increased lactate production, leading to enhanced histone lactylation and subsequent transcription of Uchl1 and several genes related to glycolysis, suggesting a glycolysis/H4K8la/UCHL1 positive feedback loop. These findings help to clarify the role of the UCHL1/PFKFB3/H4K8la loop in modulation of astrocytic metabolic reprogramming and reveal a potential target for treatment of SCI.

2025-02-21 | GSE266984 | GEO

Single-cell RNA-sequencing overviews global inflammatory response in in vitro organ cultured testes

Project description:Background: Production of functional sperms from spermatogonial stem cells in vitro is important for understanding of biological mechanisms underlying physiological spermatogenesis and for treatment of male infertility. However, comparing with the in vivo testes, in vitro spermatogenesis is severely lower efficiency. Here we describe abnormalities occurring in early stage of in vitro spermatogenesis at single cell resolution. Results: While spermatogenesis was similarly progressed between in vivo and in vitro-cultured testes, noticeable acute inflammatory response occurred right after in vitro culture of neonatal testes not only in immune cells but also non-immune testicular somatic cells. Inhibitor treatment revealed NLRP3 inflammasome signaling is key to the inflammation occurring in in vitro cultured testes We also found accumulation of damaged/dead germ cells in in vitro cultured testes, which may be due to dysfunction of sertoli cell phagocytosis. Conclusion: Our data revealed tissue-wide sterile inflammation occurring in in vitro cultured testes, in which DAMPs - NLRP3 inflammasome axis may key element. Thus, these abnormal testicular microenvironments may be a cause of low spermatogenesis efficiency of in vitro spermatogenesis.

2022-12-31 | GSE189805 | GEO

Proteomic Analysis of Spry1-Amh-cre Conditional Knockout Mouse Testis

Project description:To investigate the important role of Spry1 gene in mouse testicular development, spermatogenesis, and immune homeostasis by conditionally knocking out Spry1 in Sertoli cells of testes.

2023-08-24 | PXD044823 |

Ubiquitin C-terminal hydrolase isozyme L1 (UCHL1) is associated with shelterin complex at interstitial telomeric sites

Project description:Ubiquitin C-terminal hydrolase isozyme L1 (UCHL1) is primarily expressed in neuronal cells and neuroendocrine cells. It is a multifunctional protein involved in deubiquitination, ubiquitination, and ubiquitin homeostasis. UCHL1 has been associated with various diseases, including many cancers, but its specific roles are disputed and still generally undetermined. Herein, we demonstrate that UCHL1 is associated with genomic DNA in certain prostate cancer cell lines, including DU 145 cells derived from a brain metastatic site, and in HEK293T embryonic kidney cells with a neuronal lineage. Chromatin immunoprecipitation and sequencing revealed that UCHL1 localizes to TTAGGG repeats at telomeres and interstitial telomeric sequences, as do TRF1 and TRF2, components of the shelterin complex. A weak or transient interaction between UCHL1 and the shelterin complex was confirmed by immunoprecipitation and proximity ligation assays. UCHL1 and TERF2IP, also a component of the shelterin complex, were bound to the nuclear scaffold. UCHL1 may play a role in regulating gene expression by affecting the stabilization of the shelterin proteins or influencing nuclear targeting. As several shelterin proteins (TRF1, TRF2, POT1 and TERF2IP) are ubiquitinated, UCHL1 may have a role in regulating the stability of these proteins. UCHL1 may also regulate the nuclear location of shelterin-associated genomic regions.

2018-02-23 | GSE97111 | GEO

Genes regulated by UCHL1 in ovarian cancer cells

Project description:UCHL1 is related to apoptosis and proliferation in cancers and we sought to identify genes regulated by UCHL1

2013-01-30 | GSE43884 | GEO

Molecular identification of genes involved in testicular steroid synthesis and characterization of the response to gonadotropic stimulation in the Senegalese sole (Solea senegalensis)

Project description:In male teleosts, testicular steroids are essential hormones for the regulation of spermatogenesis and their production is regulated by pituitary gonadotropins. In the Senegalese sole (Solea senegalensis), an economically important flatfish with semi-cystic and asynchronous spermatogenesis, the endocrine mechanisms involved in the regulation of spermatogenesis, particularly regarding the production and regulation of testicular steroids, are not well understood.This study aimed at describing the transcriptomic changes taking place in the Senegalese sole testis in response to hCG stimulation in vivo. Gene expression analysis by microarray identified 90 differentially expressed genes in the testis in response to hCG administration, including genes potentially involved in steroidogenesis, progression of spermatogenesis and germ cell maturation and cytoskeletal organization. Our results provide evidence for the first time that key genes involved in the regulation of steroid production and spermatogenesis in the Senegalese sole testis are under gonadotropic control. Testes samples from saline- and hCG-injected male Senegalese sole (8 fish per group) were pooled separatedly. Pooled testicular RNAs from each group were amplified and the resulting cRNAs labelled with Cy3 and Cy5, respectively, mixed in equal amounts and hybridized to the microarray for 17 h at 60 ºC. Each hybridization was performed in duplicate.

2010-12-02 | E-GEOD-25733 | biostudies-arrayexpress

Genes regulated by UCHL1 in ovarian cancer cells

Project description:UCHL1 is related to apoptosis and proliferation in cancers and we sought to identify genes regulated by UCHL1 UCHL1 was knocked down in A2780 (A2780-shUCHL1). A2780-shUCHL1 and A2780-control were cultured in RPMI and total RNA was extracted and hybridizated on Affymetrix.GeneChip.HG-U133_Plus_2

2013-01-30 | E-GEOD-43884 | biostudies-arrayexpress

Leydig Cells in Spermatogenesis-Deficient Testes Experience Stress, but Proliferate to Enhance Testosterone Synthesis I

Project description:We investigated somatic cell dynamics in testicular tissue lacking spermatogenesis using model mice with testis-specific deletion of the histone H3 variant gene H3t. Leydig cells in testes lacking spermatogenesis led to increased testosterone synthesis that occurred alongside a high inflammatory response and oxidative stress.

2024-12-27 | GSE275209 | GEO

Leydig Cells in Spermatogenesis-Deficient Testes Experience Stress, but Proliferate to Enhance Testosterone Synthesis II

2024-12-27 | GSE275210 | GEO