Study Reveals How Fetal Circadian Rhythms Develop in Late Pregnancy

A new study has developed a method to observe the development of circadian rhythms in mouse fetuses. The research, conducted at Washington University in St. Louis, found that fetal biological clocks synchronize with the mother's daily cycle during late pregnancy, coinciding with the transfer of maternal hormones across the placenta.

How Researchers Observed the Fetal Clock

Researchers published their findings in the Journal of Biological Rhythms. To observe circadian clock activity in developing fetuses, they used a method involving genetically engineered male mice. In these mice, a luminescent protein called luciferase was attached to a key circadian clock protein.

When these males were mated with normal female mice, the tagged protein appeared in the developing fetuses but not in the mother's tissues. The pregnant mice were given water containing a chemical that reacts with luciferase to produce light. This caused the fetuses to emit light when the circadian clock protein was active. Highly sensitive cameras detected this light, allowing researchers to record the timing and identify patterns of clock protein expression.

Key Findings of the Study

• Clear day-night rhythms in clock protein expression were detected in the mouse fetuses during the last week of pregnancy, a developmental stage researchers stated is equivalent to the human third trimester.
• These fetal rhythms synchronized with the mother's rest-activity cycle.
• The synchronization coincided with the period when glucocorticoid hormones from the mother cross the placenta. These hormones, which rise and fall daily under the control of the mother's internal clock, were described by researchers as potential timing signals for the fetal clock.
• Administering synthetic glucocorticoids to the mother daily was found to accelerate the synchronization of the pups' daily rhythms to the local time.
• The study observed an association between a failure to develop circadian clock gene activity in fetuses and a failure to deliver. Researchers stated they cannot yet determine if the absence of rhythms contributes to developmental problems or simply reflects them.

"Understanding when the fetal clock begins to function helps us identify sensitive developmental windows when circadian disruption may have lasting effects and how those effects might be prevented or corrected." — Study author Nikhil Lokesh

Researcher Insights and Context

In statements provided with the study, authors commented on the implications of the work.

Senior author Erik Herzog stated: "Importantly, we found daily rhythms across the placenta from the mother to the baby before the fetus can sense light."

Lokesh also noted that over 80 percent of the world's population is exposed to artificial light at night that can disrupt daily rhythms, and that this includes pregnant people.

Circadian rhythms are daily patterns in physiological functions such as sleep and metabolism. Existing research indicates that disrupted circadian rhythms can lead to long-term negative health effects.

• Disrupting circadian rhythms during pregnancy has been linked in other studies to effects on infant sleep and daily rhythm development, and to a higher risk of mood disorders later in life.
• Synthetic glucocorticoids, which were used in the experiment, are routinely administered to pregnant women at risk of preterm birth.

Researchers suggested the findings could inform considerations about the timing of medication administration during pregnancy and help guide clinical practices and public health policies related to neonatal circadian health.