Shift work and circadian dysregulation of reproduction

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.

Keywords: circadian disruption; endocrinology; infertility; misalignment; pregnancy failure; sleep.

Figure 1

Self-selected sleep strategies for night shift work weeks in nurses. We recently characterized off-shift behavioral sleep strategies of full-time, primarily European–American nurses at Vanderbilt University Medical Center (VUMC) who completed a self-report survey (34), including a typical work-week schedule for night shift at Vanderbilt Hospital for which nurses indicated typical sleep times. (A–E) Five representative strategies for days-off (and percentage among night shift workers) were: (A) Night Stay (2.4%); (B) Nap Proxy (12.2%); (C) Switch Sleeper (49.2%); (D) No Sleep (24.3%); and (E) Incomplete Switcher (11.9%). Red indicates sleep times and dark gray indicates night shift schedule from 7:00 p.m. to 7:00 a.m. on Days D–G. Surprisingly, ∼1 out of 4 night shift nurses chose to switch between days and nights via a>24-h sleep deprivation period (the No Sleep strategy).

Figure 2

Circadian regulation of reproduction and impairment associated with shift work. Evidence suggests that the circadian clock regulates each part of the reproductive axis from timing of neuronal activity in hypothalamic neurons to the day-night variation in the release of pregnancy hormones. Dysregulation of circadian rhythms, as often occurs with shift work, results in increased risk of adverse consequences at each step of the reproductive pathway. See text for references. GnRH, gonadotropin releasing hormone; LH, luteinizing hormone; FSH, follicle stimulating hormone; ACTH, adrenocorticotropic hormone.