Gatford, K. L., Kennaway, D. J., Liu, H., Kleemann, D. O., Kuchel, T. R., & Varcoe, T. J. (2019). Simulated shift work disrupts maternal circadian rhythms and metabolism, and increases gestation length in sheep. J Physiol, 597(7), 1889–1904.
Abstract: KEY POINTS: Shift work impairs metabolic health, although its effects during pregnancy are not well understood We evaluated the effects of a simulated shift work protocol for one-third, two-thirds or all of pregnancy on maternal and pregnancy outcomes in sheep. Simulated shift work changed the timing of activity, disrupted hormonal and cellular rhythms, and impaired maternal glucose tolerance during early pregnancy. Gestation length was increased in twin pregnancies, whereas singleton lambs were lighter at a given gestational age if mothers were subjected to shift work conditions in the first one-third of pregnancy. Exposure to rotating night and day shifts, even if only in early pregnancy, may adversely affect maternal metabolic and pregnancy outcomes. ABSTRACT: Shift workers are at increased risk of developing type 2 diabetes and obesity; however, the impact during pregnancy on maternal metabolism is unknown. Using a large animal model, we assessed the impact of simulated shift work (SSW) exposure during pregnancy on maternal circadian rhythms, glucose tolerance and pregnancy outcomes. Following mating, ewes were randomly allocated to a control photoperiod (CON 12 h light, 12 h dark) or to SSW, where the timing of light exposure and food presentation was reversed twice each week for one-third, two-thirds or all of pregnancy. Maternal behaviour followed SSW cycles with increased activity during light exposure and feeding. Melatonin rhythms resynchronized within 2 days of the photoperiod shift, whereas peripheral circadian rhythms were arrhythmic. SSW impaired glucose tolerance (+29%, P = 0.019) and increased glucose-stimulated insulin secretion (+32%, P = 0.018) in ewes with a singleton fetus in early but not late gestation. SSW exposure did not alter rates of miscarriage or stillbirth, although it extended gestation length in twin pregnancies (+2.4 days, P = 0.032). Relative to gestational age, birth weight was lower in singleton progeny of SSW than CON ewes (-476 g, P = 0.016). These results have implications for the large number of women currently engaged in shift work, and further studies are required to determine progeny health impacts.
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Hsu, C. - N., & Tain, Y. - L. (2020). Light and Circadian Signaling Pathway in Pregnancy: Programming of Adult Health and Disease. Int J Mol Sci, 21(6).
Abstract: Light is a crucial environmental signal that affects elements of human health, including the entrainment of circadian rhythms. A suboptimal environment during pregnancy can increase the risk of offspring developing a wide range of chronic diseases in later life. Circadian rhythm disruption in pregnant women may have deleterious consequences for their progeny. In the modern world, maternal chronodisruption can be caused by shift work, jet travel across time zones, mistimed eating, and excessive artificial light exposure at night. However, the impact of maternal chronodisruption on the developmental programming of various chronic diseases remains largely unknown. In this review, we outline the impact of light, the circadian clock, and circadian signaling pathways in pregnancy and fetal development. Additionally, we show how to induce maternal chronodisruption in animal models, examine emerging research demonstrating long-term negative implications for offspring health following maternal chronodisruption, and summarize current evidence related to light and circadian signaling pathway targeted therapies in pregnancy to prevent the development of chronic diseases in offspring.
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Menegaux, F., Truong, T., Anger, A., Cordina-Duverger, E., Lamkarkach, F., Arveux, P., et al. (2013). Night work and breast cancer: a population-based case-control study in France (the CECILE study). Int J Cancer, 132(4), 924–931.
Abstract: Night work involving disruption of circadian rhythm was suggested as a possible cause of breast cancer. We examined the role of night work in a large population-based case-control study carried out in France between 2005 and 2008. Lifetime occupational history including work schedules of each night work period was elicited in 1,232 cases of breast cancer and 1,317 population controls. Thirteen percent of the cases and 11% of the controls had ever worked on night shifts (OR = 1.27 [95% confidence interval = 0.99-1.64]). Odds ratios were 1.35 [1.01-1.80] in women who worked on overnight shifts, 1.40 [1.01-1.92] in women who had worked at night for 4.5 or more years, and 1.43 [1.01-2.03] in those who worked less than three nights per week on average. The odds ratio was 1.95 [1.13-3.35] in women employed in night work for >4 years before their first full-term pregnancy, a period where mammary gland cells are incompletely differentiated and possibly more susceptible to circadian disruption effects. Our results support the hypothesis that night work plays a role in breast cancer, particularly in women who started working at night before first full-term pregnancy.
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Nehme, P. A., Amaral, F., Lowden, A., Skene, D. J., Cipolla-Neto, J., & Moreno, C. R. C. (2019). Reduced melatonin synthesis in pregnant night workers: metabolic implications for offspring. Medical Hypotheses, 132, 109353.
Abstract: Several novel animal studies have shown that intrauterine metabolic programming can be modified in the event of reduced melatonin synthesis during pregnancy, leading to glucose intolerance and insulin resistance in the offspring. It is therefore postulated that female night workers when pregnant may expose the offspring to unwanted health threats. This may be explained by the fact that melatonin is essential for regulating energy metabolism and can influence reproductive activity. Moreover, the circadian misalignment caused by shift work affects fertility and the fetus, increasing the risk of miscarriage, premature birth and low birth weight, phenomena observed in night workers. Thus, we hypothesize that light-induced melatonin suppression as a result of night work may alter intrauterine metabolic programming in pregnant women, potentially leading to metabolic disorders in their offspring.
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Rahman, S. A., Bibbo, C., Olcese, J., Czeisler, C. A., Robinson, J. N., & Klerman, E. B. (2019). Relationship between endogenous melatonin concentrations and uterine contractions in late third trimester of human pregnancy. J Pineal Res, 66(4), e12566.
Abstract: In humans, circulating levels of the hormone melatonin and the initiation of spontaneous labor are both higher at night than during the day. Since activation of uterine melatonin receptors can stimulate human in vitro uterine contractions and these receptors are only expressed on the uterine tissue of women in labor, we hypothesized that circulating melatonin concentrations would affect uterine contractions in vivo. We evaluated the impact of light-induced modulation of melatonin secretion on uterine contractions in women during late third-trimester (~36-39 weeks) of pregnancy in two inpatient protocols. We found a significant (p<0.05) positive linear association between circulating melatonin concentrations and the number of uterine contractions under both protocols. On average, uterine contractions increased between 1.4 to 2.1 contractions per 30 minutes for every 10 pg/ml*h increase in melatonin concentration. These findings have both basic science and clinical implications for pregnant women, since endogenous melatonin levels and melatonin receptor activity can be altered by light and/or pharmaceutical agents.
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