Interactions between heavy metals and sleep duration among pre-and postmenopausal women: A current approach to molecular mechanisms involved.

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.