Study Reveals Timing of Circadian Clock Synchronization in Fetuses

A new study published in the Journal of Biological Rhythms by researchers at Washington University in St. Louis investigates when the mammalian circadian clock begins to synchronize with local time, revealing that a mother's influence starts even before birth.

Nikhil Lokesh, a co-author of the study and a research scientist at WashU Arts & Sciences, emphasized the implications of disrupted circadian rhythms during pregnancy. He noted that such disruptions may contribute to sleep-related issues and increase the risk of anxiety and depression in infants later in life. Understanding the onset of the fetal clock's functioning could help identify crucial developmental windows where circadian disruption might be prevented or corrected.

To conduct this study, the researchers developed a method to observe the activity of the circadian clock in fetuses. They utilized genetically engineered mice that express a luminescent protein known as luciferase, which illuminates when linked to a clock protein that regulates circadian rhythms.

When a male mouse with this modification mates with a normal female, the resulting fetuses inherit the tagged clock protein. Pregnant mice were provided with water containing a chemical that reacts with luciferase, allowing researchers to observe when the fetuses’ clock proteins were active by detecting their glow.

The researchers observed that circadian patterns in the developing pups aligned with the mother’s activity cycle in the last week of pregnancy, corresponding to the human third trimester. According to Lokesh, this demonstrates that the circadian mechanisms develop early and later adapt to cues from the mother.

Erik Herzog, a senior author of the study, remarked on the synchronization of daily rhythms from the mother to the fetus, particularly as glucocorticoid hormones cross the placenta. These hormones fluctuate throughout the day, governed by the mother’s internal clock.

Interestingly, the administration of synthetic glucocorticoids to pregnant women is commonplace, often without consideration of the natural timing of these hormones. The study found that daily hormone treatment accelerated the pups' synchronization with local time. This could have implications for how medications are administered to pregnant women.

The researchers also noted a correlation between insufficient development of circadian clock genes in fetuses and delivery complications. While it remains unclear whether the absence of these rhythms contributes to developmental issues, the observation indicates a potential link between circadian clock activity and healthy fetal development.

Lokesh highlighted the need to preserve stable circadian rhythms during pregnancy, as over 80 percent of the global population currently experiences exposure to artificial light at night, which can disrupt daily rhythms.

The findings may guide medical treatments and inform clinical practices aimed at safeguarding neonatal circadian health during pregnancy. The study authors include Nikhil KL, Bates K, Sapiro E, among others, and the work was supported by NIH Grants and the March of Dimes Prematurity Research Center.