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Microplastics alter the oocyte proteome

ABSTRACT: Proteomic analysis of oocytes revealed altered abundance of proteins associated with normal oocyte function.

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ORGANISM(S): Bos Taurus (bovine)

TISSUE(S): Oocyte

SUBMITTER: Jan Bernd Stöckl

LAB HEAD: Thomas Fröhlich

PROVIDER: PXD036415 | Pride | 2026-03-12

REPOSITORIES: Pride

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Project description:Rational: Amino acid metabolism is crucial for inflammatory processes during atherogenesis. The endogenous amino acid homoarginine (HA) is a robust biomarker for cardiovascular outcome and mortality with high levels being protective. However, the underlying molecular mechanism remains elusive. Objective: We investigated the effect of HA supplementation on atherosclerotic plaque development with a particular focus on athero-inflammation. Methods and Results: Female apolipoprotein (Apo) E-deficient mice were supplemented with HA (14 mg/L) in drinking water starting two weeks before and continuing throughout a six week-course of Western-type diet (HA-treated). Control mice (Ctrl) received normal drinking water. HA supplementation led to a 2-fold increase in circulating HA concentrations. Plaque- and immunological phenotyping revealed that HA-treated mice exhibited a reduction in atherosclerosis in the aortic root as well as in the brachiocephalic trunk. A substantial decrease in lesion CD3+ T cells suggested a T cell-related effect of HA supplementation. Using mass spectrometry-based proteomics and subsequent pathway analysis together with conventional in vitro techniques such as flow cytometry, various migration and chemotaxis assays as well as super-resolution microscopy, we demonstrate that HA profoundly modulated the spatial organization of the T-cell actin cytoskeleton. Further mechanistic studies revealed an inhibition of T-cell activation and proliferation as well as a striking impairment of the migratory capacities of T cells in response to relevant chemokines by HA, all of which likely contribute to its atheroprotective effects. Conclusion: This study unravels a novel mechanism, by which the amino acid HA reduces atherosclerosis, namely the regulation of T-cell functions crucial for adaptive immunity. We identified that HA modulates the T-cell cytoskeleton and thereby mitigated important T-cell functions during atherogenesis. These findings provide a molecular explanation for the beneficial effects of HA in atherosclerotic cardiovascular disease.

Project description:Studies on gene and/or microRNA (miRNA) dysregulation in the early stages of hepatocarcinogenesis are hampered by the difficulty of diagnosing early lesions in humans. Experimental models recapitulating human hepatocellular carcinoma (HCC) are then entailed to perform this analysis. We performed miRNA and gene expression profiling to characterize the molecular events involved in the multistep process of hepatocarcinogenesis in the Resistant-Hepatocyte rat model. A high percentage of dysregulated miRNAs/genes in HCC were similarly altered in early preneoplastic lesions positive for the stem/progenitor cell marker cytokeratin-19, indicating that several HCC-associated alterations occur from the very beginning of the carcinogenic process. Our analysis also identified miRNA/gene-target networks aberrantly activated at the initial stage of hepatocarcinogenesis. Activation of the NRF2 pathway and up-regulation of the miR-200 family were among the most prominent changes. The relevance of these alterations in the development of HCC was confirmed by the observation that NRF2 silencing impaired while miR-200a overexpression promoted HCC cell proliferation in vitro. Moreover, T3-induced in vivo inhibition of the NRF2 pathway accompanied the regression of cytokeratin-19 positive nodules, suggesting that activation of this transcription factor contributes to the onset and progression of preneoplastic lesions towards malignancy. The finding that 78% of genes and 57% of dysregulated miRNAs in rat HCC have been previously associated to human HCC as well underlines the translational value of our results. Conclusions: this study indicates that most of the molecular changes found in HCC occur in the very early stages of hepatocarcinogenesis. Among these, the NRF2 pathway plays a relevant role and may represent a new therapeutic target. 20 nodules (10 weeks after initiation with DENA), 4 adenomas (10 months), 5 eHCCs (10 months) and 9 aHCCs (14 months) were dissected. 10 controls also included.

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	oocytes_1um_4.raw	Raw

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Microplastics alter the oocyte proteome

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