Sex-Specific Response of Caenorhabditis elegans to Methylmercury Toxicity
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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.
KeywordsMethylmercury Sex Male C. elegans Antioxidant Thioredoxin
This work has been supported by the National Institutes of Health [NIEHS R01ES07331 and R01ES10563; MA and ABB]. We thank the German Research Foundation (DFG) for the financial support of BO 4103/2-1 as well as the DFG Research Unit TraceAge (FOR 2558). C. elegans strains were provided by the Caenorhabditis Genetics Center (CGC, University of Minnesota, USA), which is funded by NIH Office of Research Infrastructure Programs. We would like to acknowledge Hillary Guzik for expert assistance in microscopy. The imaging was conducted in the Analytical Imaging Facility, which is funded by the NCI Cancer Grant P30CA013330.
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Conflicts of Interest
The authors declare that they have no conflict of interest.
- Hilbert ZA, Kim DH (2017) Sexually dimorphic control of gene expression in sensory neurons regulates decision-making behavior in C. elegans. Elife 6Google Scholar
- Leung YK, Ouyang B, Niu L, Xie C, Ying J, Medvedovic M, Chen A, Weihe P, Valvi D, Grandjean P, HO SM 2018. Identification of sex-specific DNA methylation changes driven by specific chemicals in cord blood in a Faroese birth cohort. Epigenetics 1–32Google Scholar
- Ruszkiewicz JA, Pinkas A, Miah MR, Weitz RL, Lawes MJA, Akinyemi AJ, Ijomone OM, Aschner M (2018) C. elegans as a model in developmental neurotoxicology. Toxicol Appl PharmacolGoogle Scholar
- Saeed U, Karunakaran S, Meka DP, Koumar RC, Ramakrishnan S, Joshi SD, Nidadavolu P, Ravindranath V (2009) Redox activated MAP kinase death signaling cascade initiated by ASK1 is not activated in female mice following MPTP: novel mechanism of neuroprotection. Neurotox Res 16:116–126CrossRefGoogle Scholar