Summary: Does a baby have a sense of time before it’s even born? A fascinating study has finally captured the moment the “biological clock” begins to tick in the womb.
By using “glow-in-the-dark” proteins to track fetal development, researchers discovered that babies develop daily rhythms during the equivalent of the human third trimester. Surprisingly, the mother’s glucocorticoid hormones (stress-related hormones) act as a chemical bridge, synchronizing the baby’s internal clock to local time long before the fetus ever sees a ray of sunlight.
Key Facts
- The “Firefly” Method: Scientists used bioluminescent proteins that glowed whenever the fetal circadian clock proteins were active. This allowed them to see the babies “ticking” inside the mother in real-time.
- Synchronization Window: Clear day-night rhythms emerged in the pups during the final week of pregnancy (the human third trimester), aligning perfectly with the mother’s rest and activity cycles.
- Hormonal Timing: Synchronization happens exactly when the mother’s glucocorticoid hormones begin crossing the placenta. These hormones naturally rise and fall throughout the day, acting as the “set” button for the baby’s clock.
- Clinical Impact of Steroids: Synthetic steroids given to prevent preterm birth were found to accelerate the baby’s clock synchronization. This suggests that the timing of when doctors give these medications could be vital for neonatal health.
- A Link to Survival: The study observed a strong link between a failing circadian clock and a failure to deliver, suggesting that a healthy “rhythm” may be a requirement for a successful birth.
Source: WUSTL
Humans and most other organisms have internal biological clocks that track the daily cycle of sunrise and sunset. These clocks help time our sleep, metabolism and other essential body functions over the course of a day, creating daily patterns called circadian rhythms.
Research shows that when these rhythms are disrupted — by jet lag, lack of sleep or irregular work schedules — people can suffer long-term negative health effects.
Scientists who study daily rhythms have long wondered about when the mammalian circadian clock starts ticking and synchronizes to local time. In a new study published in the Journal of Biological Rhythms, researchers at Washington University in St. Louis reported that a mother helps to set the biological clock for her babies while they are still in the womb.
“We know that disrupting circadian rhythms during pregnancy can affect how sleep and daily rhythms develop in infants, and these early disruptions are linked to a higher risk of mood disorders such as anxiety and depression later in life,” said Nikhil Lokesh, study author and a research scientist in biology in WashU Arts & Sciences.
“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.”
For this new study, WashU scientists developed a way to observe circadian clock activity in fetuses while they are still developing inside the womb. The scientists used genetically engineered mice in which a luminescent protein called luciferase, the same protein that makes fireflies glow, is attached to a clock protein that drives circadian rhythms.
When a male mouse carrying this modified protein mates with a normal female, the tagged clock protein appears in the developing fetuses but not in the mother’s tissues. The pregnant mice were then given drinking water laced with a chemical that reacts with luciferase to produce light. Whenever the clock protein was active in the fetuses, they glowed.
The researchers detected that fetal light using highly sensitive cameras. By recording the glow’s timing, they were able to identify clear cyclical patterns of clock protein expression in babies while they developed inside their mothers’ womb.
“We found clear day-night rhythms in the pups that synchronized to the mother’s rest-activity cycle during the last week of pregnancy, equivalent to the third trimester in humans,” Lokesh said. “This suggests that the clock machinery forms early in development and receives entraining cues from mom later.”
“Importantly, we found daily rhythms across the placenta from the mother to the baby before the fetus can sense light,” said Erik Herzog, the Viktor Hamburger Distinguished Professor in biology, senior author on the study.
The researchers found that circadian synchronization of the pups to the mother coincided with when glucocorticoid hormones from the mother cross the placenta, potentially acting as timing signals for the fetal clock. These stress-related hormones normally rise and fall over the course of the day under the control of the mother’s internal clock.
Synthetic glucocorticoids are routinely given to pregnant women at risk of preterm birth, often without considering the time of day when these hormones naturally fluctuate. The authors found that giving these steroids daily to the mother accelerated the synchronization to local time of the daily rhythms in the pups. These findings may be important when considering how and when doctors administer medications to treat pregnancy conditions.
During the study, the researchers also observed a strong association between failure to develop circadian clock gene activity in the fetuses and failure to deliver. “We cannot yet say whether the absence of rhythms contributes to developmental problems or simply reflects them,” Lokesh said. “But the observation suggests that circadian clock activity may be closely linked to healthy fetal development.”
Lokesh said the findings also highlight the importance of maintaining stable circadian rhythms during pregnancy. “Over 80 percent of the world’s population is exposed to artificial light at night that can disrupt daily rhythms, and this includes pregnant people,” he said.
“Understanding when and how the body clock starts ticking helps scientists identify sensitive developmental windows when circadian disruption may have lasting effects,” Lokesh said. “This knowledge could help guide medical treatments, inform clinical practices and shape public health policies aimed at protecting neonatal circadian health during pregnancy.”
Funding: This work was supported by National Institutes of Health Grants NINDS R01NS12116 and the March of Dimes Prematurity Research Center. KLN was supported by a fellowship from the McDonnell Center for Cellular and Molecular Neurobiology.
Key Questions Answered:
A: Light isn’t the only signal for time. The study found that mothers pass “time-stamps” to their babies through the placenta using hormones. Even though the baby can’t see the sun, their body “feels” the mother’s daily peaks in activity and hormone levels, which tells their cells when to wake up and when to rest.
A: These early rhythms are the foundation for the brain’s development. Research shows that disrupting these rhythms (via night shifts or light pollution) is linked to a higher risk of anxiety, depression, and mood disorders later in the child’s life. Maintaining a stable schedule during the third trimester is like giving the baby a head start on mental health.
A: It certainly adds weight to that advice. Over 80% of people are exposed to artificial light at night, which can confuse the mother’s clock. Since the mother is the primary “timekeeper” for the fetus, her exposure to light directly affects the baby’s ability to synchronize its own internal systems.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this pregnancy and circadian rhythm research news
Author: Leah Shaffer
Source: WUSTL
Contact: Leah Shaffer – WUSTL
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Fetoplacental circadian rhythms develop and then synchronize to the mother in utero” by Nikhil KL, Bates K, Sapiro E, Amme JL, McCarthy R, Speck SL, Vasireddy V, Roberts E, Martin-Fairey CA, Domínguez-Romero ME, Cárdenas-García SP, England SK and Herzog ED. Journal of Biological Rhythms
DOI:10.1177/07487304261435435
Abstract
Fetoplacental circadian rhythms develop and then synchronize to the mother in utero
Circadian rhythms in gene expression and hormones are ubiquitous across species and differentiated cell types, yet their developmental origins remain poorly understood. This study aimed to determine if daily rhythms can be detected in utero and if they synchronize to the mother.
We developed methods to longitudinally monitor PERIOD2 (PER2), a core circadian clock protein, from embryonic day (E)8.5 to E17.5 by restricting PER2::LUCIFERASE expression to the mouse fetoplacental unit (fetus and fetal-derived tissues).
In utero fetoplacental bioluminescence imaging showed that PER2 levels increased during pregnancy, with variable daily peak times that stabilized to early night by E15.5. Interestingly, pregnancies that did not exhibit daily in utero PER2 variation were more likely to fail.
Because maternal glucocorticoids have been implicated in fetal development and synchronizing other circadian tissues, we tested whether glucocorticoid injections could shift fetoplacental PER2 rhythms in utero.
Daily subcutaneous corticosterone injections over 5 days of late pregnancy phase-dependently shifted the fetoplacental PER2 rhythms in utero. Blocking glucocorticoid signaling in vitro reduced synchrony between maternal and fetal placenta.
We conclude that in utero daily rhythms gradually develop and synchronize with the mother prior to birth, potentially through glucocorticoid signaling.
