Title: Sex-Specific Response of Caenorhabditis elegans to Methylmercury Toxicity.
Authors: Ruszkiewicz, Joanna A; Teixeira de Macedo, Gabriel; Miranda-Vizuete, Antonio; Bowman, Aaron B; Bornhorst, Julia; Schwerdtle, Tanja; Antunes Soares, Felix A; Aschner, Michael
Published In Neurotox Res, (2019 Jan)
Abstract: Methylmercury (MeHg), an abundant environmental pollutant, has long been known to adversely affect neurodevelopment in both animals and humans. Several reports from epidemiological studies, as well as experimental data indicate sex-specific susceptibility to this neurotoxicant; however, the molecular bases of this process are still not clear. In the present study, we used Caenorhabditis elegans (C. elegans), to investigate sex differences in response to MeHg toxicity during development. Worms at different developmental stage (L1, L4, and adult) were treated with MeHg for 1 h. Lethality assays revealed that male worms exhibited significantly higher resistance to MeHg than hermaphrodites, when at L4 stage or adults. However, the number of worms with degenerated neurons was unaffected by MeHg, both in males and hermaphrodites. Lower susceptibility of males was not related to changes in mercury (Hg) accumulation, which was analogous for both wild-type (wt) and male-rich him-8 strain. Total glutathione (GSH) levels decreased upon MeHg in him-8, but not in wt. Moreover, the sex-dependent response of the cytoplasmic thioredoxin system was observed-males exhibited significantly higher expression of thioredoxin TRX-1, and thioredoxin reductase TRXR-1 expression was downregulated upon MeHg treatment only in hermaphrodites. These outcomes indicate that the redox status is an important contributor to sex-specific sensitivity to MeHg in C. elegans.
PubMed ID: 30155682
MeSH Terms: Age Factors; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Cytoplasm/drug effects; Cytoplasm/metabolism; Dopaminergic Neurons/drug effects; Dopaminergic Neurons/metabolism; Dopaminergic Neurons/pathology; Female; Glutathione/metabolism; Green Fluorescent Proteins/genetics; Green Fluorescent Proteins/metabolism; Male; Methylmercury Compounds/toxicity*; Neurodegenerative Diseases/chemically induced; Neurodegenerative Diseases/metabolism; Neurodegenerative Diseases/pathology; Sex Characteristics*; Thioredoxin-Disulfide Reductase/metabolism; Thioredoxins/metabolism