Developmental methylmercury (MeHg) exposure can have lasting consequences on neural development and motor function across the lifespan. Recent evidence for MeHg targeting of myogenic pathways has drawn attention to the possibility that developing skeletal muscle plays a role in the motor deficits stemming from early life MeHg exposure. In this study we examined a potential role for muscle in influencing MeHg developmental toxicity in offspring of female mice exposed to MeHg via drinking water. Dams had access to 0, 0.5 or 5.0 ppm MeHg chloride in drinking water from two weeks prior to mating through weaning. Blood, brain and muscle tissue was harvested from dams at weaning and pups at postnatal days (PND) 6, 21 and 60 for analysis of total Hg. Muscle tissue sections were examined with histological stains. Behavioral testing of offspring was conducted at PND 60 and included locomotor activity, inverted screen, grip strength and rotarod tests to assess motor function. Total Hg (tHg) levels in dam muscles at weaning were 1.7–3-fold higher than Hg levels in blood or brain. In PND6 male and female pups, muscle and brain tHg levels were 2 to 4-fold higher than blood tHg. Brain tHg levels decreased more rapidly than muscle tHg levels between PND 6 and 21. Premised on modeling of growth dilution, brain tissue demonstrated an elimination of tHg while muscle tissue exhibited a net uptake of tHg between PND 6 and 21. Despite overall elevated Hg levels in developing muscle, no gross morphological or cytological phenotypes were observed in muscle at PND 60. At the higher MeHg dose, grip strength was reduced in both females and males at PND 60, whereas only male specific deficits were observed in locomotor activity and inverted screen tests with marginally significant deficits on rotarod. These findings highlight a potential role for developing skeletal muscle in mediating the neuromuscular insult of early life MeHg exposure.

发育期甲基汞 (MeHg) 暴露会对整个生命周期的神经发育和运动功能产生持久影响。最近关于甲基汞靶向生肌途径的证据引起了人们的注意，即发育中的骨骼肌在生命早期接触甲基汞导致的运动缺陷中发挥着一定作用。在这项研究中，我们研究了肌肉在影响通过饮用水接触甲基汞的雌性小鼠后代的甲基汞发育毒性方面的潜在作用。从交配前两周到断奶，母鼠的饮用水中含有 0、0.5 或 5.0 ppm 的甲基汞氯化物。在断奶时的母鼠和出生后第 6、21 和 60 天 (PND) 的幼崽中采集血液、脑和肌肉组织，用于分析总汞。用组织学染色检查肌肉组织切片。在 PND 60 时对后代进行行为测试，包括运动活动、倒置屏幕、握力和旋转杆测试以评估运动功能。断奶时母鼠肌肉中的总汞 (tHg) 水平比血液或大脑中的汞水平高 1.7-3 倍。在 PND6 雄性和雌性幼崽中，肌肉和大脑 tHg 水平比血液 tHg 高 2 至 4 倍。在 PND 6 至 21 年间，脑 tHg 水平比肌肉 tHg 水平下降得更快。以生长稀释模型为前提，脑组织表现出 tHg 的消除，而肌肉组织在 PND 6 至 21 之间表现出 tHg 的净摄取。尽管整体 Hg 水平升高在发育中的肌肉中，PND 60 时在肌肉中没有观察到总体形态学或细胞学表型。 在较高的甲基汞剂量下，PND 60 时，女性和男性的握力均有所降低，而在运动活动和倒转筛选测试中仅观察到男性特定缺陷，并且旋转棒上的缺陷稍显着。这些发现强调了骨骼肌发育在介导生命早期甲基汞暴露造成的神经肌肉损伤方面的潜在作用。