Gestational jet lag predisposes to later-life skeletal and cardiac disease |
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Authors: | Inês Chaves Bram van der Eerden Ruben Boers Joachim Boers Astrid A. Streng Yanto Ridwan |
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Affiliation: | 1. Department of Molecular Genetics, University Medical Center Rotterdam, Rotterdam, The Netherlandsi.chaves@erasmusmc.nl g.vanderhorst@erasmusmc.nl;2. Department of Internal Medicine, University Medical Center Rotterdam, Rotterdam, The Netherlands;3. Department of Developmental Biology, University Medical Center Rotterdam, Rotterdam, The Netherlands;4. Department of Molecular Genetics, University Medical Center Rotterdam, Rotterdam, The Netherlands;5. Department of Vascular Surgery, University Medical Center Rotterdam, Rotterdam, The Netherlands;6. Department of Radiology &7. Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands |
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Abstract: | Circadian rhythm disturbance (CRD) increases the risk of disease, e.g. metabolic syndrome, cardiovascular disease, and cancer. In the present study, we investigated later life adverse health effects triggered by repeated jet lag during gestation. Pregnant mice were subjected to a regular light-dark cycle (CTRL) or to a repeated delay (DEL) or advance (ADV) jet lag protocol. Both DEL and ADV offspring showed reduced weight gain. ADV offspring had an increased circadian period, and an altered response to a jet lag was observed in both DEL and ADV offspring. Analysis of the bones of adult male ADV offspring revealed reduced cortical bone mass and strength. Strikingly, analysis of the heart identified structural abnormalities and impaired heart function. Finally, DNA methylation analysis revealed hypermethylation of miR17-92 cluster and differential methylation within circadian clock genes, which correlated with altered gene expression. We show that developmental CRD affects the circadian system and predisposes to non-communicable disease in adult life. |
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Keywords: | Circadian clock jet lag DOHaD developmental programming epigenetics DNA methylation |
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