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Embryonic exposure to aluminium chloride blocks the onset of spermatogenesis through disturbing the dynamics of testicular tight junctions via upregulating Slc25a5 in offspring

ABSTRACT: Embryonic exposure to aluminium chloride blocks the onset of spermatogenesis through disturbing the dynamics of testicular tight junctions via upregulating Slc25a5 in offspring

PROVIDER: PRJNA1011930 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25884966_1.fastq.gz	Fastqsanger.gz
	SRR25884966_2.fastq.gz	Fastqsanger.gz
	SRR25884967_1.fastq.gz	Fastqsanger.gz
	SRR25884967_2.fastq.gz	Fastqsanger.gz
	SRR25884968_1.fastq.gz	Fastqsanger.gz

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Embryonic exposure to aluminium chloride blocks the onset of spermatogenesis through disturbing the dynamics of testicular tight junctions via upregulating Slc25a5 in offspring

Project description:Studies reveal neurotoxicity, hepatotoxicity, and developmental and reproductive toxicity in mice exposed to aluminium (Al). However, relatively few researches are conducted to clarify the mechanism of the impact of embryonic exposure to aluminium chloride (AlCl3) on the development of the reproductive system in male offspring. Here, pregnant mice were fed AlCl3 by gavage from day 12.5 of gestation. The results showed that embryonic AlCl3 exposure disrupted testicular development and spermatogenesis by damaging the testicular structure, reducing sperm counts, and altering the expression of the tight junction (TJ) proteins between Sertoli cells (SCs). Further in vitro studies showed that AlCl3 treatment stabilized the TJ proteins Occludin and ZO-1 expression by inhibiting the ERK signaling pathway to upregulate the Slc25a5 protein, which prompted ATP production to disrupt cytoskeletal protein homeostasis. Therefore, our study provided a new mechanism for AlCl3 exposure to interfere with testicular development and spermatogenesis and implied that Slc25a5 could be a target of AlCl3 affecting cell metabolism.

2023-09-06 | GSE242190 | GEO

Loss of tight junctions disrupts gastrulation patterning and increases differentiation towards the germ cell lineage in human pluripotent stem cells

Project description:To investigate the role of tight junctions in BMP4 signaling and differentiation, we knocked down TJP1 in human pluripotent stem cells using CRISPRi, and examined gene expression via RNA sequencing of TWT (no KD) and TKD (TJP1 KD) cells in the untreated pluripotent (P) state and after BMP4 differentiation (B).

2022-09-23 | GSE213911 | GEO

Inflammation of gill epithelia in fish causes increased permeation of polar organic chemicals from OSPW via disruption of tight junctions

Project description:The epithelial cell layer that lines the fish gill controls the paracellular permeation of chemicals through tight junctions. The integrity of tight junctions can be affected by inflammation, which is likely to impact the branchial bioavailability of chemicals. In this study, we experimentally induced inflammation in the rainbow trout gill cell line RTgill-W1 via exposure to bacterial lipopolysaccharides (LPS). We then co-exposed the cells to extracts of oil sands process-affected water (OSPW), which contain a complex mixture of toxicologically relevant chemicals. Cells exposed to LPS showed a significant reduction in transepithelial electrical resistance (TEER), an indicator of tight junction integrity, after 24 h of exposure. Quantitative RT-PCR analysis determined that the abundance of transcripts of genes coding for tight junction proteins (Claudin 28b and 10e) was significantly decreased in cells exposed to 20, 50, and 100 mg L-1 LPS. Chemical analysis revealed a significant increase in permeation of constituents of OSPW across the gill cell epithelial layer at all studied LPS concentrations. These in vitro findings were confirmed in vivo in rainbow trout fingerlings exposed to both LPS and 10% OSPW for 48 h, which similarly resulted in an increase in chemical uptake relative to fish exposed to OSPW alone. This research demonstrated that inflammation of gill epithelia and the resulting disruption of tight junction integrity could lead to significantly greater uptake of potentially harmful chemicals from the environment, which has important implications for risk assessment.

2022-02-28 | GSE182953 | GEO

mRNA profiling of NMuMG mouse mammary epithelial cells incubated for 4 weeks in the presence of aluminium chloride vs controls incubated in parallel in the presence of the same dilution of solvent (H2O) alone

Project description:Salts of aluminium, a chemical element devoid of biological function, are added to many industrial products of frequent use because of aluminium's chemical versatility. As a result of lifetime exposure, aluminium accumulates in several organs including the mammary gland. At concentrations in the range of those measured in the breast of women living in industrialised countries, aluminium chloride transforms human and mouse mammary epithelial cells in vitro. These results challenge the safety commonly ascribed to aluminium and suggest that it could be a human carcinogen. NMuMG is a spontaneously immortalised, non tumorigenic mouse mammary epithelial cell line originally derived from NAMRU mice that, following chronic culture in the presence of aluminium - in the form of AlCl3 x 6H2O - becomes able to form tumors and metastasis in NOD-scid and nude mice. As a part of our investigations on the mechanisms by which aluminium might transform mammary epithelial cells, we analysed the mRNA profile of NMuMG cells incubated for 4 weeks - a time duration that precedes cellular transformation - in the presence of aluminium or the corresponding untreated controls cultured in parallel, by cDNA microarray. We used the Clariom S microarray from Thermofisher, that covers more than 20'000 well annotated mRNAs.

2020-11-30 | E-MTAB-9764 | biostudies-arrayexpress

mRNA profiling of HC11 mouse mammary epithelial cells incubated for 4 weeks in the presence of aluminium chloride vs controls incubated in parallel in the presence of the same dilution of solvent (H2O) alone

Project description:Salts of aluminium, a chemical element devoid of biological function, are added to many industrial products of frequent use because of aluminium's chemical versatility. As a result of lifetime exposure, aluminium accumulates in several organs including the mammary gland. At concentrations in the range of those measured in the breast of women living in industrialised countries, aluminium chloride transforms human and mouse mammary epithelial cells in vitro. These results challenge the safety commonly ascribed to aluminium and suggest that it could be a human carcinogen. HC11 is a spontaneously immortalised, non tumorigenic mouse mammary epithelial cell line originally derived from Balb/c mice that, following chronic culture in the presence of aluminium - in the form of AlCl3 x 6H2O - becomes able to form tumors and metastasis in the immunocompetent and immunocompatible strain Balb/cByJ. As a part of our investigations on the mechanisms by which aluminium might transform mammary epithelial cells, we analysed the mRNA profile of HC11 cells incubated for 4 weeks - a time duration that precedes cellular transformation - in the presence of aluminium or the corresponding untreated controls cultured in parallel, by cDNA microarray. We used the Clariom S microarray from Thermofisher, that covers more than 20'000 well annotated mRNAs.

2020-11-30 | E-MTAB-9763 | biostudies-arrayexpress

mRNA profiling of HC11 mouse mammary epithelial cells transformed in vitro by long-term incubation in the presence of aluminium chloride vs controls incubated in parallel in the presence of the same dilution of solvent (H2O) alone.

Project description:Salts of aluminium, a chemical element devoid of biological function, are added to many industrial products of frequent use because of aluminium's chemical versatility. As a result of lifetime exposure, aluminium accumulates in several organs including the mammary gland. At concentrations in the range of those measured in the breast of women living in industrialised countries, aluminium chloride transforms human and mouse mammary epithelial cells in vitro. These results challenge the safety commonly ascribed to aluminium and suggest that it could be a human carcinogen. HC11 is a spontaneously immortalised, non tumorigenic mouse mammary epithelial cell line originally derived from Balb/c mice that, following chronic culture in the presence of aluminium - in the form of AlCl3 x 6H2O - becomes able to form tumors and metastasis in the immunocompetent and immunocompatible strain Balb/cByJ. As a part of our investigations on the mechanisms by which aluminium might transform mammary epithelial cells, we analysed the mRNA profile of HC11 cells transformed in vitro by aluminium or the corresponding untreated controls cultured in parallel by cDNA microarray. We used the Clariom S microarray from Thermofisher, that covers more than 20'000 well annotated mRNAs.

2020-11-30 | E-MTAB-9723 | biostudies-arrayexpress

Analysis of transcriptome response of rhizobia to aluminium toxicity

Project description:Purpose: High throughput sequencing has revolutionized methods of microbial pathway analysis in response to various envoronmental stimuli. The aim of this study was to determine mechanisms in which Rhizobium phaseoli employ towards tolerance or resistance to aluminium toxicity through RNA sequencing. Methods: Total RNA was extracted from bacteria treated with aluminium after 48 hours with trizol and sequenced with illumina’s Miseq at Novogene Corporation Inc. U.K. After QC, reads were aligned to the genome with bowtie2 and differential expression performed with DESeq2. Results: Sequencing resulted to about 6.7-9.0 M reads that aligned to all the four plasmids and one chromosome of R. phaseoli genome. Most enriched genes were found localized in the membrane of the bacteria. Conclusion: The membrane of R. phaseoli is possibly the target site for toxicity and tolerance against aluminium toxicity. This is the first time such a study is described.

2022-01-17 | GSE193556 | GEO

mRNA profiling of NMuMG mouse mammary epithelial cells transformed in vitro by long-term incubation in the presence of aluminium chloride vs controls incubated in parallel in the presence of the same dilution of solvent (H2O) alone. Referred to as \\"NMuMG series I\\" in the citing manuscript (Mandriota et al., submitted).

Project description:Salts of aluminium, a chemical element devoid of biological function, are added to many industrial products of frequent use because of aluminium's chemical versatility. As a result of lifetime exposure, aluminium accumulates in several organs including the mammary gland. At concentrations in the range of those measured in the breast of women living in industrialised countries, aluminium chloride transforms human and mouse mammary epithelial cells in vitro. These results challenge the safety commonly ascribed to aluminium and suggest that it could be a human carcinogen. NMuMG is a spontaneously immortalised, non tumorigenic mouse mammary epithelial cell line originally derived from NAMRU mice that, following chronic culture in the presence of aluminium - in the form of AlCl3 x 6H2O - becomes able to form tumors and metastasis in NOD-scid and nude mice. As a part of our investigations on the mechanisms by which aluminium might transform mammary epithelial cells, we analysed the mRNA profile of NMuMG cells transformed in vitro by aluminium or the corresponding untreated controls cultured in parallel by cDNA microarray. We used the Clariom S microarray from Thermofisher, that covers more than 20'000 well annotated mRNAs. The cell culture experiment analyzed in this microarray is referred to as \\"NMuMG series I\\" in the citing manuscript (Mandriota et al., submitted).

2020-11-30 | E-MTAB-9733 | biostudies-arrayexpress

mRNA profiling of NMuMG mouse mammary epithelial cells transformed in vitro by long-term incubation in the presence of aluminium chloride vs controls incubated in parallel in the presence of the same dilution of solvent (H2O) alone. Referred to as \"NMuMG series III\" in the citing manuscript (Mandriota et al., submitted).

Project description:Salts of aluminium, a chemical element devoid of biological function, are added to many industrial products of frequent use because of aluminium's chemical versatility. As a result of lifetime exposure, aluminium accumulates in several organs including the mammary gland. At concentrations in the range of those measured in the breast of women living in industrialised countries, aluminium chloride transforms human and mouse mammary epithelial cells in vitro. These results challenge the safety commonly ascribed to aluminium and suggest that it could be a human carcinogen. NMuMG is a spontaneously immortalised, non tumorigenic mouse mammary epithelial cell line originally derived from NAMRU mice that, following chronic culture in the presence of aluminium - in the form of AlCl3 x 6H2O - becomes transformed in vitro. In this specific experiment - referred to as NMuMG series III in the citing manuscript (Mandriota et al., submitted) - transformation was assessed in vitro, by the soft agar assay. As a part of our investigations on the mechanisms by which aluminium might transform mammary epithelial cells, we analysed the mRNA profile of NMuMG cells transformed in vitro by aluminium or the corresponding untreated controls cultured in parallel by cDNA microarray. We used the Clariom S microarray from Thermofisher, that covers more than 20'000 well annotated mRNAs.

2020-11-30 | E-MTAB-9735 | biostudies-arrayexpress

Functional analysis of membrane-associated scaffolding tight junction (TJ) proteins in tumorigenic characteristics of B16-F10 mouse melanoma cells.

Project description:Tight junction (TJ) proteins (Tjps), Tjp1 and Tjp2, are tight junction-associated scaffold proteins that bind to the transmembrane proteins of tight junctions and the underlying cytoskeleton. In this study, we first analyzed the tumorigenic characteristics of B16-F10 melanoma cells, including cell proliferation, migration, invasion, metastatic potential, and the expression patterns of related proteins, after the CRISPR-Cas9-mediated knockout (KO) of Tjp genes. The proliferation of Tjp1 and Tjp2 KO cells significantly increased in vitro. Other tumorigenic characteristics, including migration and invasion, were significantly enhanced in Tjp1 and Tjp2 KO cells.

2024-08-01 | GSE240070 | GEO

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