New research indicates that a mother plays a direct role in setting the biological clock of her unborn child, with daily rhythms beginning to form in the fetus well before birth. This process, governed by internal biological mechanisms that align with the 24-hour day, helps regulate essential functions such as sleep, metabolism, and hormone release. Scientists have long sought to understand when this internal timing system becomes active in mammals and how it synchronizes with the external environment.
A study published in the Journal of Biological Rhythms reveals that in mice, the fetal circadian clock begins to show clear day-night patterns during the final week of pregnancy, which corresponds to the third trimester in humans. Researchers used genetically modified mice in which a luminescent protein—luciferase, the same compound that causes fireflies to glow—was attached to a core clock protein. This allowed them to visualize the timing of gene activity in real time as the fetuses developed inside the womb.
The findings show that the fetus does not rely on light perception to establish these rhythms. Instead, the synchronization occurs through chemical signals passed from mother to child across the placenta. Specifically, the rise and fall of glucocorticoid hormones—natural steroids involved in stress response and metabolism—appear to act as a timing cue. These hormones follow a daily rhythm under the control of the mother’s own biological clock and were found to cross the placenta at the precise moment when fetal clock gene activity began to align with the maternal day-night cycle.
“We found clear day-night rhythms in the pups that synchronized to the mother’s rest-activity cycle during the last week of pregnancy,” said Nikhil Lokesh, a research scientist in biology at Washington University in St. Louis and lead author of the study. “This suggests that the clock machinery forms early in development and receives entraining cues from mom later.”
Erik Herzog, a professor of biology at the same institution and senior author on the study, emphasized that the connection occurs before the fetus can sense light. “Importantly, we found daily rhythms across the placenta from the mother to the baby before the fetus can sense light,” he noted, highlighting the role of hormonal signaling over visual input in early circadian development.
The study similarly examined the impact of synthetic glucocorticoids, which are commonly administered to pregnant women at risk of preterm birth to accelerate fetal lung development. When given to the mother mice, these synthetic steroids accelerated the synchronization of the fetal clock to the external time environment. This finding raises questions about the timing of such treatments, suggesting that administering them in alignment with the mother’s natural hormone rhythms might better support healthy circadian development in the fetus.
Beyond timing, the researchers observed a significant association between the absence of rhythmic clock gene activity in the fetus and complications in pregnancy. Pregnancies in which the fetal circadian clock failed to develop proper daily patterns were more likely to result in unsuccessful delivery. While the researchers caution that they cannot yet determine whether disrupted rhythms cause developmental issues or merely reflect them, the correlation suggests a close link between circadian health and fetal viability.
“We cannot yet say whether the absence of rhythms contributes to developmental problems or simply reflects them,” Lokesh stated. “But the observation suggests that circadian clock activity may be closely linked to healthy fetal development.”
The implications extend beyond the laboratory. With over 80% of the global population exposed to artificial light at night—a known disruptor of circadian rhythms—pregnant individuals may be particularly vulnerable to disturbances that could affect fetal development. Lokesh emphasized that maintaining stable daily rhythms during pregnancy, including consistent sleep-wake cycles and minimizing nighttime light exposure, could support the healthy emergence of the infant’s biological clock.
Understanding when and how the fetal clock begins to tick allows scientists to identify sensitive windows in development when circadian disruption might have lasting consequences. This knowledge could inform clinical practices, such as optimizing the timing of medications during pregnancy, and guide public health efforts aimed at protecting maternal and neonatal circadian health.
The research was supported by the National Institutes of Health and the March of Dimes Prematurity Research Center. Additional support for Lokesh came through a fellowship from the McDonnell Center for Cellular and Molecular Neurobiology at Washington University in St. Louis.
As scientists continue to explore the origins of circadian rhythms in early life, this work underscores the profound influence of the maternal environment on the developing child—even before birth. By recognizing the role of internal timing signals passed from mother to fetus, healthcare providers may better support the foundation of lifelong health from the earliest stages of development.
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