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      Shift Work and Circadian Dysregulation of Reproduction

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          Abstract

          Health impairments, including reproductive issues, are associated with working nights or rotating shifts. For example, shift work has been associated with an increased risk of irregular menstrual cycles, endometriosis, infertility, miscarriage, low birth weight or pre-term delivery, and reduced incidence of breastfeeding. Based on what is known about circadian regulation of endocrine rhythms in rodents (and much less in humans), the circadian clock is an integral regulatory part of the reproductive system. When this 24-h program is disordered by environmental perturbation (such as shift work) or genetic alterations, the endocrine system can be impaired. The purpose of this review is to explore the hypothesis that misalignment of reproductive hormones with the environmental light-dark cycle and/or sleep-wake rhythms can disrupt menstrual cycles, pregnancy, and parturition. We highlight the role of the circadian clock in regulating human reproductive physiology and shift work-induced pathology within each step of the reproductive axis while exploring potential mechanisms from the animal model literature. In addition to documenting the reproductive hazards of shift work, we also point out important gaps in our knowledge as critical areas for future investigation. For example, future studies should examine whether forced desynchronization disrupts gonadotropin secretion rhythms and whether there are sleep/wake schedules that are better or worse for the adaptation of the reproductive system to shift work. These studies are necessary in order to define not only whether or not shift work-induced circadian misalignment impairs reproductive capacity, but also to identify strategies for the future that can minimize this desynchronization.

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          Most cited references86

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          The genetics of mammalian circadian order and disorder: implications for physiology and disease.

          Circadian cycles affect a variety of physiological processes, and disruptions of normal circadian biology therefore have the potential to influence a range of disease-related pathways. The genetic basis of circadian rhythms is well studied in model organisms and, more recently, studies of the genetic basis of circadian disorders has confirmed the conservation of key players in circadian biology from invertebrates to humans. In addition, important advances have been made in understanding how these molecules influence physiological functions in tissues throughout the body. Together, these studies set the scene for applying our knowledge of circadian biology to the understanding and treatment of a range of human diseases, including cancer and metabolic and behavioural disorders.
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            Rotating night shifts and risk of breast cancer in women participating in the nurses' health study.

            Melatonin shows potential oncostatic action, and light exposure during night suppresses melatonin production. There is little information, however, about the direct effect of night work on the risk of cancer. We investigated the effect of night work in breast cancer. We examined the relationship between breast cancer and working on rotating night shifts during 10 years of follow-up in 78 562 women from the Nurses' Health Study. Information was ascertained in 1988 about the total number of years during which the nurses had worked rotating night shifts with at least three nights per month. From June 1988 through May 1998, we documented 2441 incident breast cancer cases. Logistic regression models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs), adjusted for confounding variables and breast cancer risk factors. All statistical tests were two-sided. We observed a moderate increase in breast cancer risk among the women who worked 1-14 years or 15-29 years on rotating night shifts (multivariate adjusted RR = 1.08 [95% CI = 0.99 to 1.18] and RR = 1.08 [95% CI = 0.90 to 1.30], respectively). The risk was further increased among women who worked 30 or more years on the night shift (RR = 1.36; 95% CI = 1.04 to 1.78). The test for trend was statistically significant (P =.02). Women who work on rotating night shifts with at least three nights per month, in addition to days and evenings in that month, appear to have a moderately increased risk of breast cancer after extended periods of working rotating night shifts.
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              Health disorders of shift workers.

              The effects of shift work on physiological function through disruption of circadian rhythms are well described. However, shift work can also be associated with specific pathological disorders. This article reviews the evidence for a relationship between specific medical disorders and working at night or on shift systems. The strongest evidence exists for an association with peptic ulcer disease, coronary heart disease and compromised pregnancy outcome.
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                Author and article information

                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                05 June 2013
                07 August 2013
                2013
                : 4
                : 92
                Affiliations
                [1] 1Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham , Birmingham, AL, USA
                [2] 2Department of Cell and Developmental and Integrative Biology, University of Alabama at Birmingham , Birmingham, AL, USA
                [3] 3Department of Biological Sciences, Vanderbilt University , Nashville, TN, USA
                Author notes

                Edited by: James Olcese, Florida State University, USA

                Reviewed by: Ted H. Elsasser, United States Department of Agriculture, USA; Jari Rossi, University of Helsinki, Finland

                *Correspondence: Carl Hirschie Johnson, Department of Biological Sciences, Vanderbilt University, 465 21st Avenue South, Nashville, TN 37235, USA e-mail: carl.h.johnson@ 123456vanderbilt.edu

                This article was submitted to Frontiers in Systems and Translational Endocrinology, a specialty of Frontiers in Endocrinology.

                Article
                10.3389/fendo.2013.00092
                3736045
                23966978
                fa4163bb-3f93-4f7b-9d62-231ec51eb697
                Copyright © 2013 Gamble, Resuehr and Johnson.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 May 2013
                : 10 July 2013
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 94, Pages: 9, Words: 7978
                Categories
                Endocrinology
                Review Article

                Endocrinology & Diabetes
                endocrinology,pregnancy failure,misalignment,sleep,circadian disruption,infertility

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