Does consumption of a high-fructose diet during pregnancy and lactation exacerbate the effects of maternal exposure to cadmium on development and metabolic function of mouse offspring?

Exposures to pollutants rarely occur in isolation, often coexisting with other environmental stressors such as diet and may be particularly insidious in early life. The aim of this study was to examine effects of maternal exposure to cadmium (Cd) and consumption of a high-fructose diet (HFrD) on development of mouse offspring. Female CD-1 mice were administered either 0.5 or 5 ppm Cd in drinking water with or without an approximate 60% fructose diet for 3 weeks prior to mating. Dams were maintained on the same treatment until postnatal day (PND) 16. Cadmium concentrations in maternal, fetal, and neonatal liver increased in a concentration-dependent manner irrespective of diet. Endpoints known to be associated with Cd or HFrD adverse effects were assessed longitudinally in offspring from birth to young adulthood, including growth trajectory, pubertal development, body composition, glycemic tolerance and hepatic lipid accumulation. Maternal exposure to either Cd or HFrD alone significantly advanced onset of puberty, hypoglycemia, and reduced adiposity in adulthood. HFrD rarely exacerbated metal-initiated effects in most of the endpoints examined outside of pubertal timing. Because of chronic effects attributed to Cd or HFrD on metabolic function (e.g. glucose tolerance), transcriptomics and gene methylation analyses were performed on livers from neonatal and adult offspring. Data were largely consistent with phenotypic findings. In summary, maternal exposure to Cd or HFrD alone perturbed growth and development, producing long-lasting changes in metabolic function in adult offspring. HFrD did not appear to significantly exaggerate adverse outcomes attributed to metal exposure in the endpoints examined.

污染物暴露极少单独发生，通常会与饮食等其他环境应激因素共存，且在生命早期阶段往往具有格外隐匿的危害性。本研究旨在探究母体暴露于镉（Cd）以及摄入高果糖饮食（HFrD）对小鼠子代生长发育的影响。在交配前3周，对雌性CD-1小鼠通过饮水给予0.5 ppm或5 ppm的镉，并分别配合或不配合约60%果糖含量的饮食干预。孕鼠持续接受相同的干预方案直至仔鼠出生后第16天（postnatal day, PND 16）。母鼠、胎鼠以及新生仔鼠肝脏中的镉浓度均呈浓度依赖性升高，且不受饮食干预的影响。本研究对从出生到青年成年阶段的子代小鼠，纵向评估了与镉或高果糖饮食不良反应相关的已知实验终点指标，包括生长轨迹、青春期发育、身体成分、血糖耐量以及肝脏脂质蓄积情况。母体单独暴露于镉或单独摄入高果糖饮食，均会显著提前子代青春期启动时间、引发成年期低血糖，并降低成年子代的体脂含量。除青春期发育时间这一指标外，在其余绝大多数被评估的实验终点中，高果糖饮食极少会加剧镉暴露所引发的效应。鉴于镉或高果糖饮食对代谢功能（如血糖耐量）具有慢性影响，本研究对新生仔鼠与成年子代的肝脏组织开展了转录组学（transcriptomics）与基因甲基化（gene methylation）分析。分析数据与表型观测结果整体相符。综上，母体单独暴露于镉或单独摄入高果糖饮食，均会扰乱子代的生长发育，对成年子代的代谢功能造成持久改变。在本次评估的实验终点中，高果糖饮食并未显著加剧镉暴露所导致的不良结局。