Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression profiling of mouse ing2 -/- mice with spermatogenic arrest and infertility

ABSTRACT: Expression profiling of mouse ing2 -/- testis vs WT reveals gene expression differences consistent with spermatogenic arrest and infertility. Ing2 is indispensable for male germ cell development in mice. While mice deficient for Ing2 were born and grew without apparent abnormalities, male, but not female, were infertile, consistent with the highest expression of Ing2 in testes in wild-type mice and in humans. Histological and DNA content analyses in Ing2-/- testes revealed a spermatogenesis arrest at meiotic phase and enhanced apoptosis associated with increased p53, resulting in a decline in mature spermatozoa, which became more severe in older age. HDAC1 accumulation and core histone deacetylation at pachytene stage were impaired in Ing2-/- testes, suggesting that the recruitment of HDAC1 by Ing2 plays a critical role in spermatogenesis. This study establishes Ing2 as a novel mammalian regulator of spermatocyte differentiation, which coordinates spermatogenesis stage-specific histone modifications. This study has implications in understanding human male infertility. Testis from WT and Ing2 KO mice at 2-3 months of age where analyzed for differences in gene expression.

ORGANISM(S): Mus musculus

SUBMITTER: Ana Robles

PROVIDER: E-GEOD-18610 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Expression profiling of mouse ing2 -/- mice with spermatogenic arrest and infertility

Project description:Expression profiling of mouse ing2 -/- testis vs WT reveals gene expression differences consistent with spermatogenic arrest and infertility. Ing2 is indispensable for male germ cell development in mice. While mice deficient for Ing2 were born and grew without apparent abnormalities, male, but not female, were infertile, consistent with the highest expression of Ing2 in testes in wild-type mice and in humans. Histological and DNA content analyses in Ing2-/- testes revealed a spermatogenesis arrest at meiotic phase and enhanced apoptosis associated with increased p53, resulting in a decline in mature spermatozoa, which became more severe in older age. HDAC1 accumulation and core histone deacetylation at pachytene stage were impaired in Ing2-/- testes, suggesting that the recruitment of HDAC1 by Ing2 plays a critical role in spermatogenesis. This study establishes Ing2 as a novel mammalian regulator of spermatocyte differentiation, which coordinates spermatogenesis stage-specific histone modifications. This study has implications in understanding human male infertility.

2010-11-19 | GSE18610 | GEO

MALDI-IMS combined with shotgun proteomics identify and localize new factors in male infertility

Project description:Spermatogenesis is a complex multi-step process involving intricate interactions between different cell types in the male testis. Disruption of these interactions results in infertility. Combination of shotgun tissue proteomics with MALDI imaging mass spectrometry is markedly potent in revealing topological maps of molecular processes within tissues. Here, we use a combinatorial approach on a characterized mouse model of hormone induced male infertility to uncover misregulated pathways. Comparative testicular proteome of wildtype and mice overexpressing human P450 aromatase (AROM+) with pathologically increased estrogen levels unravels gross dysregulation of spermatogenesis and emergence of pro-inflammatory pathways in AROM+ testis. In situ MS allowed us to localize misregulated proteins/peptides to defined regions within the testis. Results suggest that infertility is associated with substantial loss of proteomic heterogeneity, which define distinct stages of seminiferous tubuli in healthy animals. Importantly, considerable loss of mitochondrial factors, proteins associated with late stages of spermatogenesis and steroidogenic factors characterise AROM+ mice. Thus, the novel proteomic approach pinpoints in unprecedented ways the disruption of normal processes in testis and provides a signature for male infertility.

2021-01-07 | PXD022870 | Pride

Expression data from P15 mouse testes control and Ikbkap-knockout mice

Project description:Ikbkap/Elp1 regulates genes involved in spermatogenesis. Ikbkap deficiency causes male infertility by disrupting meiotic progression. In this dataset, we include the expression data for control and Ikbkap-knockout mouse testis. We analyzed the gene expression in control and Ikbkap-knockout testes using the the Affymetrix MoGene-1_0-st-v1 platform. Three replicates per genotype.

2013-12-31 | E-GEOD-42230 | biostudies-arrayexpress

Proteome and phosphoproteome of Wip1-knockout mouse testis

Project description:Spermatogenesis plays an important role in the mammalian testis, involving in the complex processes of mitosis, meiosis, and spermiogenesis. Spermatogenesis may also be disrupted in the absence of the immunological and ‘fence’ functions of the BTB, resulting in male subfertility or infertility. Mice lacking wild-type p53-induced phosphatase 1 (Wip1) display male reproductive organ defects, but the molecular mechanisms underlying these abnormalities remain unclear. We explored the function of Wip1 in spermatogenesis and fertility by examining differences in the expressed testis proteome and phosphoproteome between Wip1-deficient and wild-type mice using a proteomics approach. 90 proteins and 178 phosphoproteins were differentially regulated between these two groups of mice. These results suggested that proinflammatory cytokines may impair the blood–testis barrier dynamics by decreasing the expression of junction-associated proteins, which effect could be partially responsible for the subfertility and spermatogenesis defects in Wip1-knockout mice.

2022-03-01 | PXD008277 | Pride

Integrative proteomic and phosphoproteomic profiling of testis from Wip1-knockout mice: insights into mechanisms of reduced fertility

Project description:Spermatogenesis plays an important role in the mammalian testis, involving in the complex processes of mitosis, meiosis, and spermiogenesis. Spermatogenesis may also be disrupted in the absence of the immunological and ‘fence’ functions of the BTB, resulting in male subfertility or infertility. Mice lacking wild-type p53-induced phosphatase 1 (Wip1) display male reproductive organ defects, but the molecular mechanisms underlying these abnormalities remain unclear. We explored the function of Wip1 in spermatogenesis and fertility by examining differences in the expressed testis proteome and phosphoproteome between Wip1-deficient and wild-type mice using a proteomics approach. Among a total of 6872 proteins and 4280 phosphorylation sites on 1614 proteins identified in our analysis, 58 proteins and 159 phosphorylation sites on 141 proteins were differentially regulated between these two groups of mice. These results suggested that proinflammatory cytokines may impair the blood–testis barrier dynamics by decreasing the expression of junction-associated proteins, which effect could be partially responsible for the subfertility and spermatogenesis defects in Wip1-knockout mice.

2018-11-02 | PXD009220 | Pride

RNF20 is required for male fertility through H2B ubiquitination in Sertoli cells

Project description:Spermatogenesis is an essential process to generate male gametes in vertebrates, and it has become an important social health problem caused by spermatogenesis disorder. However, the molecular mechanism underlying spermatogenesis, particularly epigenetic modification in Sertoli cells of testis, remain elusive. In this study we generated Rnf20 conditional knockout mice by recombinant mothed, and only to find that Rnf20 knockout in Sertoli cells led to male infertility.

2023-04-12 | GSE225232 | GEO

Comprehensive Analysis of the Testis from Wild-Type and Alkbh5- Knockout Mice Using Single-Cell RNA Sequencing

Project description:The RNA demethylase ALKBH5 is regarded as the “eraser” in N6-methyladenosine (m6A) modification. ALKBH5 deficiency has been reported to cause male infertility in mice; however, the mechanisms that confer disruption of spermatogenesis are not completely clear. In this study, we profiled testis samples from wild-type (WT) and Alkbh5 knockout (KO) mice by single-cell RNA sequencing (scRNA-seq). We obtained scRNA-seq data of 5596 and 6816 testis cells from a WT and KO mouse, respectively. Genetic profile differences between the groups were detected at different germ cell development stages, from the development of spermatogonia to sperm cells, as well as in macrophages, Sertoli cells, and Leydig cells. We further focused on differentially expressed genes related to spermatogenesis in germ cells and somatic cells (Sertoli cells and Leydig cells), and identified their functions and associated pathways by gene ontology enrichment analysis, such as chromatin-related functional pathways and Dnah8 gene, This study providing the first scRNA-seq profiles of the testes of ALKBH5-deficient mice highlights that ALKBH5 is an important transcription factor for germ cell development and spermatogenesis with new molecular mechanistic insight. These findings can provide the basis for further research into the causes and treatment of male infertility.

2021-12-09 | GSE190396 | GEO

Expression data from Shp2f/f and SCSKO mice testis

Project description:The ability of male reproduction is seriously dependent on Sertoli cells. However, the mechanisms governing the functional integrity of Sertoli cells remained largely unexplored. Tyrosine phosphatase protein Shp2 is expressed in germ, Leydig and Sertoli cells of mice testes. But the physiological role of Shp2 in the spermatogenesis was not fully understood. Thus, we conditionally deleted Shp2 gene in Sertoli cells using two transgenic models, and demonstrated that Shp2 deficiency caused infertility, excessive differentiation of SSCs and abnormal BTB in mice. To further discover the underlying mechanism of Shp2 regulation, we collected the mRNA of testes from wild type or knockout mice at 16.5 fetal day, Postnatal 3 days, 1 weeks, 2 weeks, and then screened the gene expression. Testis tissues from Shp2f/f and SCSKO mice were for RNA extraction and hybridization on Affymetrix microarrays.

2015-05-14 | E-GEOD-68829 | biostudies-arrayexpress

Identification of a damaging variant rs35033974 associated with idiopathic male infertility through degradation of TEX101 protein and its transient interactome

Project description:Human TEX101 is a testis-specific cell membrane protein expressed exclusively in male germ cells and a validated biomarker of male infertility. TEX101 was suggested to function as a cell surface chaperone of numerous proteins involved in sperm migration and sperm-egg interaction. However, the precise functional roles of human TEX101 in spermatogenesis and fertilization are unknown. Here, we show that a common homozygous variant rs35033974 of TEX101 (G99V) with ~1% frequency in the general population may be associated with idiopathic male infertility. Spermatozoa from patients with homozygous rs35033974 exhibited near-complete degradation of variant G99V TEX101 protein and concomitant degradation of its interactome, as revealed by proteomic measurements. Substantially reduced levels of numerous testis-specific membrane proteins involved in sperm migration and sperm-oocyte fusion (including LY6K, IZUMO3 and ADAM29) were confirmed in spermatozoa of men with homozygous G99V variant. These men were previously diagnosed with idiopathic male infertility or oligospermia and failed the treatment by intrauterine insemination. Collectively, these data may facilitate diagnostics of idiopathic male infertility, provides a rational for selection of male infertility treatments and validate TEX101 and its interactome as targets to develop non-hormonal male contraceptives.

2024-11-02 | MSV000096278 | MassIVE