Department of Molecular Pharmacology, Albert Einstein College of Medicine Bronx, New York, NY, USA.
Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
Neurotox Res. 2019 Jan;35(1):208-216. doi: 10.1007/s12640-018-9949-4. Epub 2018 Aug 28.
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.
甲基汞（MeHg）是一种丰富的环境污染物，长期以来一直被认为会对动物和人类的神经发育产生不利影响。一些来自流行病学研究的报告以及实验数据表明，这种神经毒素对性别具有特异性易感性；然而，这一过程的分子基础仍不清楚。在本研究中，我们使用秀丽隐杆线虫（C. elegans）来研究发育过程中对 MeHg 毒性的性别差异。用 MeHg 处理处于不同发育阶段（L1、L4 和成虫）的线虫 1 小时。致死率测定表明，当处于 L4 阶段或成虫期时，雄性线虫对 MeHg 的抗性明显高于雌雄同体线虫。然而，MeHg 对雄性和雌雄同体线虫中退化神经元的数量没有影响。雄性线虫的低易感性与汞（Hg）积累的变化无关，野生型（wt）和雄性丰富的 him-8 品系的 Hg 积累情况相似。在 him-8 中，总谷胱甘肽（GSH）水平在 MeHg 作用下降低，但在 wt 中没有降低。此外，还观察到细胞质硫氧还蛋白系统的性别依赖性反应-雄性线虫中硫氧还蛋白 TRX-1 的表达显著升高，而只有在雌雄同体线虫中，TRXR-1 的表达在 MeHg 处理后下调。这些结果表明，氧化还原状态是秀丽隐杆线虫对 MeHg 性别特异性敏感性的重要贡献因素。
