Summary: Can a developing baby sense time before birth? A new study captures when the fetal “biological clock” starts to tick and how it becomes aligned with the mother’s daily cycle while still in the womb.
Using bioluminescent proteins that glow when core clock molecules are active, researchers tracked circadian activity in fetuses and found that daily rhythms emerge during the equivalent of the human third trimester. The team also identified maternal glucocorticoid hormones — stress-linked hormones that cycle across the day — as a likely chemical signal that synchronizes the fetal clock to local time long before the fetus is exposed to light.
Key Facts
- The “firefly” tracking method: Scientists attached a luciferase reporter to a core clock protein so that fetal tissues emitted light when clock genes were active. This allowed continuous, real-time observation of fetal circadian activity inside the pregnant mouse.
- Synchronization window: Robust day–night rhythms appeared in the fetuses during the last week of gestation in mice, a period comparable to the human third trimester, and these rhythms matched the mother’s rest–activity schedule.
- Hormonal entrainment: The onset of maternal glucocorticoids crossing the placenta coincided with the time fetuses began to show synchronized daily rhythms, indicating these hormones may act as timing cues for the developing clock.
- Clinical implications of synthetic steroids: Administration of synthetic glucocorticoids, commonly used to reduce complications from preterm birth, accelerated fetal clock synchronization. This raises the possibility that the timing of such treatments could influence neonatal circadian development.
- Association with delivery outcomes: Pregnancies in which fetuses did not show normal circadian gene rhythms were more likely to fail to carry to term, suggesting a link between fetal clock activity and healthy pregnancy progression.
Source: WUSTL
Background: Humans and most animals maintain internal biological clocks that align physiology and behavior to the 24-hour cycle of light and dark. These clocks coordinate sleep, metabolism and many other daily processes, collectively known as circadian rhythms. Disrupting these rhythms — by shift work, irregular sleep, jet lag or nighttime light exposure — has been associated with adverse health effects across the lifespan.
Researchers at Washington University in St. Louis sought to determine when the mammalian circadian oscillator begins to function and how it becomes synchronized to the external day–night cycle. Their findings, published in the Journal of Biological Rhythms, show that the mother helps entrain the fetal circadian system in utero.
“Disrupting circadian rhythms during pregnancy can alter how sleep and daily rhythms develop after birth, and those early disturbances are linked to higher risk of mood disorders later in life,” said Nikhil Lokesh, a study author and research scientist in biology. Pinpointing when the fetal clock activates reveals sensitive developmental windows during which circadian disruption could have lasting effects and suggests opportunities to prevent or correct those effects.
To track fetal clock activity, the team used genetically engineered mice where the luciferase enzyme — the same protein that makes fireflies glow — was fused to PERIOD2 (PER2), a core circadian protein. When males carrying the PER2::luciferase allele bred with normal females, the fetuses expressed the tagged protein while the mother’s tissues did not. Pregnant females drank water containing a luciferase substrate so fetal tissues produced light whenever PER2 was active.
Sensitive cameras recorded that in utero bioluminescence over several days, allowing the researchers to observe daily oscillations of clock protein expression across fetal and fetoplacental tissues. The recordings revealed that PER2 expression increased as pregnancy progressed and began to show stable early-night peaks by embryonic day 15.5 in mice.
Senior author Erik Herzog noted that these daily rhythms emerged across the placenta before the fetus has access to environmental light cues, supporting the idea that maternal signals — rather than fetal light perception — set the initial phase of the fetal clock.
Because maternal glucocorticoids follow a daily pattern and are known to influence fetal development, the investigators tested whether glucocorticoid signaling could shift fetal rhythms. Daily corticosterone injections given during late pregnancy produced phase-dependent shifts in fetoplacental PER2 rhythms in utero. Blocking glucocorticoid receptors in vitro also reduced synchrony between maternal and fetal placental tissues, supporting a role for these hormones in timing fetal clocks.
The observation that synthetic glucocorticoids accelerated rhythm synchronization highlights an important clinical consideration: the timing of steroid administration during pregnancy may affect when and how a fetal circadian system is established. Further study will be needed to determine whether such timing affects long-term outcomes for infants.
The research team also reported a correlation between absence of detectable fetal PER2 rhythms and pregnancies that failed to progress, though it remains unclear whether disrupted circadian activity contributes to developmental problems or is a marker of underlying issues. Nevertheless, the link suggests fetal clock activity is closely tied to healthy development.
Lokesh emphasized the broader public-health message: maintaining stable daily cycles during pregnancy is likely important. With more than 80 percent of people exposed to artificial light at night worldwide, pregnant individuals may be at risk of circadian disruption that could influence fetal timing cues.
“Understanding when and how the body clock begins operating in the fetus helps identify critical windows when disruption could have lasting effects,” Lokesh said. “This information can inform clinical practice, guide timing of medical treatments and shape public-health advice intended to protect 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 received fellowship support from the McDonnell Center for Cellular and Molecular Neurobiology.
Key Questions Answered:
A: Light is not the only timekeeper. The study shows that the mother transmits daily timing signals across the placenta — notably rhythmic hormones and activity-related cues — so fetal cells receive information about when to be active or rest even before exposure to environmental light.
A: Early daily rhythms provide a scaffold for brain and physiological development. Disruption of those rhythms—through night-shift work, light at night, or other circadian disturbances—has been linked in prior research to higher risks of mood and sleep disorders later in life. Preserving stable rhythms in late pregnancy may support healthier postnatal outcomes.
A: The findings reinforce the recommendation to minimize nighttime light exposure because maternal circadian cues set fetal timing. Reducing light at night and keeping regular sleep–wake schedules are practical steps to support maternal and fetal circadian health.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full.
- Additional context was provided by the editorial staff.
About this pregnancy and circadian rhythm research news
Author: Leah Shaffer
Source: WUSTL
Contact: Leah Shaffer – WUSTL
Image: Image 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 widespread across species and cell types, but their developmental origins are not fully understood. This study asked whether daily rhythms can be measured in utero and whether they become synchronized to the mother.
The investigators developed a longitudinal imaging approach to monitor PERIOD2 (PER2) by restricting PER2::LUCIFERASE expression to the fetoplacental unit from embryonic day 8.5 to 17.5 in mice. In utero bioluminescence imaging showed increasing PER2 levels during pregnancy, with daily peak times that became more stable and shifted to early night by E15.5. Pregnancies lacking in utero PER2 variation were more prone to failure.
Because maternal glucocorticoids have established roles in fetal development and in synchronizing other circadian tissues, the team tested whether corticosterone injections could shift fetoplacental PER2 rhythms. Daily subcutaneous corticosterone over five days of late pregnancy produced phase-dependent shifts in fetal rhythms in utero. Blocking glucocorticoid signaling in vitro reduced maternal–fetal placental synchrony.
The authors conclude that daily rhythms develop in utero and then synchronize with the mother prior to birth, with glucocorticoid signaling as a plausible mechanism for that synchronization.