Methylmercury exposure-induced reproductive effects are mediated by dopamine in Caenorhabditis elegans

Abstract

Methylmercury (MeHg) is a neurotoxicant that exists in the natural environment, which level can be greatly increased because of human activity. MeHg exposures have the risk of being detrimental to the development of the nervous system. Studies on MeHg toxicity have largely focused on the mechanisms of its neurotoxicity following developmental exposures. Additionally, reproductive toxicity of developmental MeHg exposures has been noted in rodent models. The model organism Caenorhabditis elegans (C. elegans) is a self-fertilizing animal which has a short lifespan around 20 days. Most C. elegans are hermaphrodites that can generate both sperm and oocytes. To investigate the effects of developmental MeHg exposures on the reproduction in C. elegans, larvae stage 1 worms were exposed to MeHg (0, 0.01 or 0.05 μM) for 24 h. The laid eggs and oocytes were compared during each day at adult stages for 6 days. We showed that MeHg exposure significantly induced an increased number of eggs in day 1 adults without an effect on the timing of egg laying or the total number of eggs or oocytes over the 6-day period. The expression of dat-1 and cat-2 and dopamine levels were increased in worms exposed to MeHg. Supplementation with 100 μM dopamine recapitulated the effect of MeHg on the number of eggs present in day 1 adults. Furthermore, the effect of MeHg on the number of eggs was abrogated in the cat-2 mutant worms CB1112. The number of oocytes in the 6-day adult stages was decreased by MeHg in the dat-1 mutant RM2702. MeHg exposures did not change the mating rate or the number of offspring from mating. Combined, these novel findings show that developmental exposure to low levels of MeHg has limited effects on the reproduction in C. elegans. Furthermore, our data support a modulatory role of dopamine in MeHg-induced effects on reproduction in this model system.

Keywords: Caenorhabditis elegans; Dopamine; Methylmercury; Reproduction; Tyrosine hydroxylase.