In accordance with research presented at the 25th European Congress of Endocrinology, female mice can be subjected to shift work-like patterns for just four weeks before their biological clocks are thrown off and their ability to conceive is diminished. The research advances our knowledge of how circadian disturbances affect female fertility and may eventually help develop preventative measures for women who work irregular hours.
The body's internal clocks, which are synced to a 24-hour period primarily by changes in light throughout days, produce the circadian rhythm. The sleep-wake cycle, hormone secretion, digestion, and reproduction are just a few of the biological processes and functions that these clocks control, but they are readily thrown off by inappropriate light exposure, such as light at night.
The 'master biological clock' is located in the suprachiasmatic nuclei, a small region in the centre of the brain called the hypothalamus. The hypothalamus is also the regulatory centre for reproductive function by acting on the pituitary gland - attached to the bottom of the hypothalamus - which in turn regulates ovarian activity to promote ovulation. Numerous studies in both mice and humans indicate a negative impact on female reproduction when the circadian rhythm is disrupted. However, the underlying mechanisms are not yet fully understood.
Researchers from the Institute of Cellular and Integrative Neurosciences (INCI) and the University of Strasbourg have previously shown that shift work-like patterns for several weeks lead to a reduced pregnancy rate in female mice. Now, in this study, the researchers mimicked long-term shift work conditions in female mice by constantly shifting the light-dark cycle, delaying and advancing light exposure by 10 hours across four weeks, and found that the massive release of the pituitary hormone called luteinising hormone - which triggers ovulation - was abolished, subsequently reducing fertility in these mice.
"The decreased fertility is due to an alteration of the master circadian clock signalling towards the hypothalamic reproductive circuit," said lead researcher Marine Simonneaux. "Specifically, our research shows that four weeks of chronic shift exposure impairs the transmission of light information from the master biological clock to the kisspeptin neurons, known to drive the timing of the pre-ovulatory luteinising hormone surge."
The next step for research will be to look at whether other additional internal clocks are altered after shift work-like patterns. "The circadian rhythm not only requires proper functioning of the master biological clock, but also a synchronised activity of numerous secondary clocks found in other brain areas and peripheral organs, including reproductive organs," said Ms Simonneaux. "Understanding the precise mechanisms by which circadian disruption alters the reproductive function is important, as it may pave the way for potential preventive and therapeutic interventions to reduce some of the negative effects of shift work on women's fertility."
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