Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, jeonnam, 57922, Republic of Korea.
Environ Pollut. 2023 Jan 1;316(Pt 1):120607. doi: 10.1016/j.envpol.2022.120607. Epub 2022 Nov 5.
The effects of heavy metals (cadmium, lead, and mercury) and their mixtures on sleep duration in pre-and postmenopausal women, particularly the molecular mechanisms, remain unknown. Here, we assessed the interaction between heavy metals and sleep duration among pre-and postmenopausal women (n = 1134). Furthermore, molecular mechanisms related to sleep disorders induced by studied heavy metals were further analyzed to support the previous findings. We found that serum lead levels were positively related to weekend and weekday sleep duration in premenopausal women. There were interactions between serum lead and mercury and menopausal status for sleep duration. Serum lead and mercury levels were shown to be inversely related to sleep duration in postmenopausal women. Despite the lack of statistically significant associations between mixed heavy metals and sleep duration, there were increasing trends in premenopausal women's sleeping patterns and decreasing trends in postmenopausal women's sleeping patterns. In silico analysis, IL1B, hsa-21-5p, hsa-887-3p, hsa-877-3p, and NR4A1 were identified as the most relevant genes, miRNAs, and transcription factors linked with sleep disorders induced by combined heavy metals (cadmium, lead, and mercury). Furthermore, "type 1 melanocortin receptor binding," "endocrine hormone secretion," "interleukin-1 receptor antagonist activity," "altered melanocortin system," and "sleep wake disorders" were identified as the predominant molecular mechanisms involved in the pathophysiology of sleep disorders induced by the studied heavy metals. Cut off point values and miRNA sponge templates for heavy metal exposure levels relevant to sleep disorders in pre- and postmenopausal women were reported. Future research is needed to verify our findings and provide insight into the molecular processes of long-term mixed heavy metal exposure in various populations, such as children and the elderly.
重金属（镉、铅和汞）及其混合物对绝经前和绝经后妇女睡眠持续时间的影响，尤其是分子机制，目前尚不清楚。在这里，我们评估了重金属与绝经前和绝经后妇女（n=1134）睡眠持续时间之间的相互作用。此外，还进一步分析了与研究重金属引起的睡眠障碍相关的分子机制，以支持先前的发现。我们发现，血清铅水平与绝经前妇女周末和工作日的睡眠持续时间呈正相关。血清铅和汞与绝经状态之间存在与睡眠持续时间有关的相互作用。血清铅和汞水平与绝经后妇女的睡眠持续时间呈负相关。尽管混合重金属与睡眠持续时间之间没有统计学上显著的关联，但绝经前妇女的睡眠模式呈上升趋势，绝经后妇女的睡眠模式呈下降趋势。计算机分析鉴定出与混合重金属引起的睡眠障碍相关的最相关基因、miRNA 和转录因子有 IL1B、hsa-21-5p、hsa-887-3p、hsa-877-3p 和 NR4A1。此外，“1 型黑色素皮质素受体结合”、“内分泌激素分泌”、“白细胞介素-1 受体拮抗剂活性”、“黑色素皮质素系统改变”和“睡眠-觉醒障碍”被确定为与研究重金属引起的睡眠障碍相关的主要分子机制。报告了与绝经前和绝经后妇女睡眠障碍相关的重金属暴露水平的切点值和 miRNA 海绵模板。需要进一步的研究来验证我们的发现，并深入了解不同人群（如儿童和老年人）长期混合重金属暴露的分子过程。
