Shift Work Disrupts Circadian Regulation of the Transcriptome in Hospital Nurses

• Published in: Journal of biological rhythms 2019-04, Vol.34 (2), p.167-177
• Main Authors: Resuehr, David, Wu, Gang, Johnson, Russell L., Young, Martin E., Hogenesch, John B., Gamble, Karen L.
• Format: Article
• Language: English
• Subjects: Adult; Body Temperature; Chronobiology Disorders - etiology; Chronobiology Disorders - genetics; Circadian Rhythm; Circadian rhythms; Clock gene; Cortisol; DNA microarrays; DNA-directed RNA polymerase; Endocytosis; Female; Gene expression; Gene Expression Regulation; Gene regulation; Genomes; Hospitals; Humans; Hydrocortisone - blood; Leukocytes, Mononuclear; Locomotion; Locomotor activity; Medical personnel; Melatonin; Melatonin - blood; Microarray Analysis; Misalignment; Night shifts; Nurses; Nurses - statistics & numerical data; Occupational health; Period 1 protein; Peripheral blood mononuclear cells; Rhythm; Ribonucleic acid; RNA; RNA polymerase; Shift work; Shift Work Schedule - adverse effects; Signal transduction; Sleep; Sleep Disorders, Circadian Rhythm - etiology; Transcription; Transcriptome; Transduction; Variability; Workers; Working conditions; Young Adult
• ISSN: 0748-7304; 1552-4531
• DOI: 10.1177/0748730419826694

Circadian misalignment between sleep and behavioral/feeding rhythms is thought to lead to various health impairments in shift workers. Therefore, we investigated how shift work leads to genome-wide circadian dysregulation in hospital nurses. Female nurses from the University of Alabama at Birmingham (UAB) Hospital working night shift (n = 9; 29.6 ± 11.4 y) and day shift (n = 8; 34.9 ± 9.4 y) participated in a 9-day study measuring locomotor activity and core body temperature (CBT) continuously. Additionally, cortisol and melatonin were assayed and peripheral blood mononuclear cells (PBMCs) were harvested for RNA extraction every 3 h on a day off from work. We saw phase desynchrony of core body temperature, peak cortisol, and dim light melatonin onset in individual night-shift subjects compared with day-shift subjects. This variability was evident even though day- and night-shift nurses had similar sleep timing and scheduled meal times on days off. Surprisingly, the phase and rhythmicity of the expression of the clock gene, PER1, in PBMCs were similar for day-shift and night-shift subjects. Genome-wide microarray analysis of PBMCs from a subset of nurses revealed distinct gene expression patterns between night-shift and day-shift subjects. Enrichment analysis showed that day-shift subjects expressed pathways involved in generic transcription and regulation of signal transduction, whereas night-shift subjects expressed pathways such as RNA polymerase I promoter opening, the matrisome, and endocytosis. In addition, there was large variability in the number of rhythmic transcripts among subjects, regardless of shift type. Interestingly, the amplitude of the CBT rhythm appeared to be more consistent with the number of cycling transcripts for each of the 6 subjects than was melatonin rhythm. In summary, we show that shift-work patterns affect circadian alignment and gene expression in PBMCs.