Four weeks of shift work could disrupt women’s biological clocks, says study.

Previous studies have shown that younger women who work late night shifts and are exposed to that environment for long durations might possibly need fertility treatment, as this may impair fertility and gestational success. But does that also hold true for women who are doing shift work?

Possibly, but the underlying mechanisms of these changes have not yet been fully understood.

A new study presented at the 25th European Congress of Endocrinology has attempted to decode how a shift in the sleep-wake cycle affects fertility in female mice. 

The team carried out their experiments in an animal-based model by constantly shifting the Circadian rhythm, the 24-hour internal clock in our brain that tells us to sleep when it’s dark, wake when it’s light, and regulates the cycle of alertness

These clocks regulate various biological functions and processes, including the sleep-wake cycle, hormone secretion, digestion, and reproduction, but can easily be disrupted by inappropriate light exposure, such as light at night, said the press release.

“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 lead researcher Marine Simonneaux. 

The team changed the patterns of light exposure that the female mice were receiving by 10 hours across four weeks. They found that the hormone which triggers ovulation, luteinizing hormone, was abolished in the mice over the weeks, thus reducing their fertility.

Simonneaux added, “The decreased fertility is due to an alteration of the master circadian clock signalling towards the hypothalamic reproductive circuit. 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.”

Researchers from the Institute of Cellular and Integrative Neurosciences (INCI) and the University of Strasbourg presented their findings at the 25th European Congress of Endocrinology in Istanbul, Turkey.

Hinting at more research to come, which will focus on whether other additional internal clocks are altered after shift work-like patterns, Simonneaux added, “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.”

Study abstract:

In female mammals, the timing of the preovulatory LH surge depends on the combination of the positive estrogen feedback and a circadian signal which synchronizes the LH surge with the transition between the resting and active period at the end of the follicular phase, when arousal is maximal. Previous results have demonstrated that a functional biological clock, located in the suprachiasmatic nucleus (SCN), is required for optimal female fertility. In this context, we have investigated the consequences a chronodisruptive environment could have on the female mammals’ gonadotropic axis using a female mouse model of shiftwork. This is a relevant issue since an increasing number of women are working in non-standard work schedules in our modern 24 h/7 d society, and shift work is associated with reproductive deficits. Adult female mice were either kept in regular light/dark schedules or exposed to a model of shift work conditions (3 weeks rotation a 10-hour phase advance for three days and a 10-hour phase delay for four days). Daily rhythms in SCN vasopressin-containing neurons, kisspeptin neurons, LH secretion on the day of proestrus, as well as fertility parameters, were compared between both groups of mice. The chronodisruptive protocol reduces the number of the vasopressin neurons known to transmit the daily information to the kisspeptin neurons, abolished activation of kisspeptin neurons typically observed at the light/dark transition, and reduced the amplitude and altered the timing of the preovulatory LH surge. Furthermore, when female mice exposed to chronic shift are mated with a male, the number of gestation is reduced as compared to those observed in control female mice. Our results indicate that chronic shift desynchronizes the hypothalamic-pituitary-ovarian axis. Notably, chronic exposure to disrupted light/dark cycles impairs the vasopressin-induced daily activation of kisspeptin neurons which can explain the altered LH secretion and the reduced fertility in female mice. In future experiments, we will investigate whether peripheral clocks within the gonadotropic axis are also altered by chronic shift. Altogether, these experiments will provide a better understanding of circadian disruption’s potential on the daily reproductive rhythms of female mammals.