Iron regulatory protein 1 deficient mice exhibit hypospermatogenesis
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ABSTRACT:
PROVIDER: PRJNA1142461 | ENA |
REPOSITORIES: ENA
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Project description:Imbalances in testicular iron levels are linked to compromised sperm production and male infertility. Iron regulatory proteins (IRP) 1 and 2 play crucial roles in cellular iron regulation. We investigated the role of IRP1 on spermatogenesis using Irp1-deficient mice (Irp1-/-). Histological analysis of the testis of Irp1-/- mice revealed hypospermatogenesis with a significant reduction in the number of elongated spermatids and daily sperm production compared to wild-type (WT) mice. Flow cytometry of germ cells from WT and Irp1-/- mice showed reduction in spermatocytes, round and elongated spermatids, which was confirmed by histological and immunofluorescence quantification. Finally, stage VIII of spermatogenesis, crucial for spermatid maturation, was less frequent in Irp1-/- testicular cross-sections. Hypospermatogenesis worsened with age despite unchanged intratesticular iron levels. Mechanistically, this was due to increased oxidative stress indicated by elevated 8-Oxoguanine (8-OxoG) levels, a DNA lesion resulting from reactive oxygen species (ROS). Furthermore, bulk RNA-seq data indicated compromised DNA damage repair and cell cycle processes, including mitosis and meiosis, which may explain hypospermatogenesis.Our results suggest that IRP1 deletion leads to hypospermatogenesis due to impaired cell cycle progression, decreased DNA damage repair capacity and oxidative damage. Altogether, this study uncovers a role for IRP1, independent of traditional iron regulation mechanisms.
2024-12-30 | GSE273580 | GEO
Project description:Mouse Iron Distribution Dynamics
Dynamic model of iron distribution in mice. This model attempts to fit the radioiron tracer data from Lopes et al. 2010 for mice fed iron deficient and rich diets by adjusting the rate of iron intake (vDiet) and the hepcidin synthesis rate (vhepcidin) independently for each experiment. All other parameters are those that provide the best fit for the adequate diet.
This model includes the radioiron tracer species.
Differences in parameter values between deficient, rich, and adequate diets:
Diet
vDiet
vhepcidin
Adequate
0.00377422
1.7393e-08
Deficient
0
8.54927e-09
Rich
0.00415624
2.30942e-08
2024-09-02 | BIOMD0000000734 | BioModels
Project description:Transcriptional profile of whole roots of wild-type and pye-1 mutants exposed to 24 hours -Fe were generated Global population increases and climate change underscore the need for better comprehension of how plants acquire and process nutrients such as iron. A systems biology approach was taken to elucidate novel regulatory mechanisms involved in plant responses to iron deficiency (-Fe). Using cell-type specific transcriptional profiling we identified a pericycle-specific iron deficiency response, and a previously uncharacterized transcription factor, POPEYE (PYE), that plays an important role in this response. Functional analysis of PYE suggests that it positively regulates growth and development under iron deficient conditions. ChIP-on-chip analysis and transcriptional profiling reveal that PYE helps maintain iron homeostasis by directly and indirectly regulating the expression of ferric reductases, metal ion transporters, iron storage proteins, and other key iron homeostasis genes. In addition to PYE, we also identified a second protein BRUTUS (BTS), which appears to negatively regulate the response to iron deficiency. BTS is a unique putative E3 ligase protein, with metal ion binding and DNA binding domains. PYE and BTS are tightly co-regulated and physically interact with PYE paralogs, one of which is thought to positively regulate expression of genes involved in iron homeostasis. We propose that iron content is sensed within the pericycle where PYE, perhaps in conjunction with BTS and other regulatory proteins, is then activated to control a regulatory network involved in maintaining proper iron distribution in plants. Keywords: Expression analysis To determine how loss of PYE expression affects the transcriptional profile of whole roots, pye-1 mutants and wild-type seeds were germinated under standard growth conditions then transferred to standard media (control, MS media) or iron deficient media (-Fe, 0.3mM Ferrozine in MS media containing no ferrous sulfate). After 24 hours of exposure to +Fe or -Fe whole roots were collected and analyzed.
2010-10-12 | E-GEOD-21443 | biostudies-arrayexpress
Project description:Mouse Iron Distribution Dynamics
Dynamic model of iron distribution in mice. This model includes only normal iron with the parameters that fit the data from Lopes et al. 2010 for mice fed a deficient iron diet.
This model does not include the radioiron tracer species. It is appropriate to study the properties in conditions where no tracers are used (for example for steady state analysis).
2024-09-02 | BIOMD0000000737 | BioModels
Project description:Transcriptional profile of whole roots of wild-type and pye-1 mutants exposed to 24 hours -Fe were generated Global population increases and climate change underscore the need for better comprehension of how plants acquire and process nutrients such as iron. A systems biology approach was taken to elucidate novel regulatory mechanisms involved in plant responses to iron deficiency (-Fe). Using cell-type specific transcriptional profiling we identified a pericycle-specific iron deficiency response, and a previously uncharacterized transcription factor, POPEYE (PYE), that plays an important role in this response. Functional analysis of PYE suggests that it positively regulates growth and development under iron deficient conditions. ChIP-on-chip analysis and transcriptional profiling reveal that PYE helps maintain iron homeostasis by directly and indirectly regulating the expression of ferric reductases, metal ion transporters, iron storage proteins, and other key iron homeostasis genes. In addition to PYE, we also identified a second protein BRUTUS (BTS), which appears to negatively regulate the response to iron deficiency. BTS is a unique putative E3 ligase protein, with metal ion binding and DNA binding domains. PYE and BTS are tightly co-regulated and physically interact with PYE paralogs, one of which is thought to positively regulate expression of genes involved in iron homeostasis. We propose that iron content is sensed within the pericycle where PYE, perhaps in conjunction with BTS and other regulatory proteins, is then activated to control a regulatory network involved in maintaining proper iron distribution in plants. Keywords: Expression analysis
2010-10-12 | GSE21443 | GEO
Project description:Microarray analysis of pancreatic tissue comparing gene expression in rats fed an iron deficient or iron loaded diet vs. iron adequate diet. Goal was to determine changes in gene expression in response to iron status. 2 separate two-condition experiments: iron deficient (FeD) vs. iron adequate (FeA), and iron overload (FeO) vs. iron adequate (FeA). Performed in dye-switched duplicates. Samples pooled (n=6).
2013-02-27 | E-GEOD-44699 | biostudies-arrayexpress
Project description:Background: Cellular iron homeostasis is regulated by iron regulatory proteins (IRP1 and IRP2) that sense iron levels (and other metabolic cues) and modulate mRNA translation or stability via interaction with iron regulatory elements (IREs). IRP2 is viewed as the primary regulator in liver, yet our previous datasets showing diurnal rhythms for certain IRE-containing mRNAs suggest a nuanced temporal control mechanism. The purpose of this study is to gain insights into the daily regulatory dynamics across IRE-bearing mRNAs, specific IRP involvement, and underlying systemic and cellular rhythmicity cues in mouse liver. Results: We uncover high-amplitude diurnal oscillations in the regulation of key IRE containing transcripts in liver, compatible with maximal IRP activity at the onset of the dark phase. Although IRP2 protein levels also exhibit some diurnal variations and peak at the light-dark transition, ribosome profiling in IRP2-deficient mice reveals that maximal repression of target mRNAs at this time-point still occurs. We further find that diurnal regulation of IRE-containing mRNAs can continue in the absence of a functional circadian clock as long as feeding is rhythmic. Conclusions: Our findings suggest temporally controlled redundancy in IRP activities, with IRP2 mediating regulation of IRE-containing transcripts in the light phase and redundancy, conceivably with IRP1, at dark onset. Moreover, we highlight the significance of feeding-associated signals in driving rhythmicity. Our work highlights the dynamic nature and regulatory complexity in a metabolic pathway that had previously been considered well-understood.
2024-05-01 | GSE243134 | GEO
Project description:Microarray analysis of pancreatic tissue comparing gene expression in rats fed an iron deficient or iron loaded diet vs. iron adequate diet. Goal was to determine changes in gene expression in response to iron status.
2013-02-27 | GSE44699 | GEO
Project description:12-week-old rats, iron-replete or iron-deficient. Three groups of each condition. 230A and 230B chips used with cRNA derived from jejunal scrapes.
2007-11-11 | E-GEOD-2269 | biostudies-arrayexpress
Project description:Firstly, cell senescence and anti-oxidant genes were down-regulated by iron deficient mice and iron-specific chelator deferoxamine (DFO) using a DNA microarray. Our data suggested that down-regulation of anti-oxidant genes and cell senescence gene induced oxidative stress in iron-deficient and -specific chelated condition.
2018-01-26 | GSE109656 | GEO