Shift work, jet lag, and female reproduction

Abstract

Circadian rhythms and "clock gene" expression are involved in successful reproductive cycles, mating, and pregnancy. Alterations or disruptions of biological rhythms, as commonly occurs in shift work, jet lag, sleep deprivation, or clock gene knock out models, are linked to significant disruptions in reproductive function. These impairments include altered hormonal secretion patterns, reduced conception rates, increased miscarriage rates and an increased risk of breast cancer. Female health may be particularly susceptible to the impact of desynchronizing work schedules as perturbed hormonal rhythms can further influence the expression patterns of clock genes. Estrogen modifies clock gene expression in the uterus, ovaries, and suprachiasmatic nucleus, the site of the primary circadian clock mechanism. Further work investigating clock genes, light exposure, ovarian hormones, and reproductive function will be critical for indentifying how these factors interact to impact health and susceptibility to disease.

Figure 1

The hypothalamus-pituitary-gonadal axis regulates reproductive cycles in female mammals. Increasing levels of estrogens released from the ovaries feedback onto the hypothalamus. When estrogen stimulation reaches a threshold, gonadotropin releasing hormone (GnRH) neurons release their product into the blood stream. GnRH acts on the pituitary to trigger a surge of luteinizing hormone (LH) which then induces ovulation. In rodents, the suprachiasmatic nucleus (SCN) of the hypothalamus provides an additional signal which regulates the timing of reproductive events. Shift work schedules, jet lag, and sleep deprivation can perturb the daily (circadian) rhythms in reproduction and “clock gene” expression. Clock gene expression has been detected in the SCN, GnRH neurons and female reproductive tissues. Estrogen can influence the pattern of expression of gene expression in some of these tissues (solid arrows). Estrogen also influences the rhythmic expression of clock-controlled outputs such as activity and body temperature (dashed arrow).