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Micronutrient deficiencies, environmental exposures and severe malaria: Risk factors for adverse neurodevelopmental outcomes in Ugandan children

ABSTRACT:

ORGANISM(S): Homo Sapiens

TISSUE(S): Cerebrospinal Fluid

DISEASE(S): Environmental Exposure,Micronutrient Deficiency

PROVIDER: ST000877 | MetabolomicsWorkbench |

REPOSITORIES: MetabolomicsWorkbench

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Proteomic dissection of the impact of environmental exposures on mouse seminal vesicle function

Project description:The seminal vesicles are an integral part of the male accessory gland system, and are responsible for producing a complex array of bioactive moieties that support gamete function and promote reproductive success. However, despite their physiological significance, the biology of the seminal vesicles remains poorly defined. Here, we exploit an established reproductive toxicant model, where mice were administered acrylamide (25 mg/kg bw/day) or control each morning for 5 consecutive days prior to collecting seminal vesicle tissue 72 h following the final injection, to complete the first proteomic assessment of mouse seminal vesicles. A total of 5,013 proteins were identified in the core seminal vesicle proteome with bioinformatics analysis of identifying cell proliferation, transcript/protein production and cellular death and survival pathways as prominent biological processes. Comparison of our acrylamide to control seminal vesicle proteome revealed 311 differentially regulated (-1.5 ≤ FC ≥ 1.5, p ≤ 0.05, 205 up-regulated, 106 down-regulated) proteins with immunoblotting analysis confirming proteomic data. Pathways that initiate protein synthesis to promote cellular survival were prominent amongst the dysregulated cellular pathways and RICTOR (Z-score = -3.64, p = 6.69E-07) was a top-ranked upstream driver. Oxidative stress was implicated as a contributor to protein changes with acrylamide leading to a significant increase in 8-OHdG in epithelial cells (5-fold increase, p = 0.016). Direct effects of acrylamide on seminal vesicle function were observed through a reduction in seminal vesicle secretion weight and overall protein content. Together these finding support the emerging concept that in addition to sperm, paternal exposures exert significant influence on the seminal vesicles, and identify new pathways to develop targeted interventions with which to manipulate fertility and reproductive outcomes.

2021-05-31 | PXD021998 | Pride