Summary: Maternal biological rhythms support the development of the fetal suprachiasmatic nuclei.
During fetal development, before the biological clock starts ticking on its own, genes within the fetus’s developing clock respond to rhythmic behavior in the mother, according to a new study in PLOS Biology by Alena Sumová and colleagues of the Czech Academy of Sciences in Prague.
The findings contribute to our understanding of the development of the internal clock, and may have implications for the treatment of premature babies.
The suprachiasmatic nuclei (SCN), structures within the hypothalamus, are the master timekeepers for the body. Rhythmic activity of genes in SCN cells in turn governs the activity of many other genes both locally and elsewhere in the body, ultimately influencing a wide variety of circadian rhythmic behavior, including feeding and sleeping.
But that rhythmic gene activity begins in earnest relatively late in fetal development, raising the question of whether maternal influences entrain gene activity within the SCN prior to birth.
To explore that question, the authors compared the pattern of gene activity in SCN tissue from fetuses developing within pregnant rats kept in the dark, under two sets of conditions. Control rats had intact SCNs and free access to food, while lesioned rats had their SCNs disrupted but their access to food was limited to eight hours per day, to impose a circadian rhythm in their activity that their SCNs could no longer sustain.
They found that, within SCNs of both sets of fetuses, there was a very small set of genes whose timing pattern differed between the two groups, and a much larger set whose activity oscillated in sync with each other.
Many of these latter genes could be assigned to two major processes—neuronal development and neuronal function, likely reflecting in the first case the ongoing development of the SCN as it wires itself up for mature function, and in the second case the earliest manifestation of that function.
“Our data reveal that in development in the fetal suprachiasmatic nuclei, maternal stimuli may substitute for an absent inter-cellular web of synapses and drive cell-population rhythms before the SCN clock fully matures,” Sumová said.
Because the rats used in these experiments have a gestational period of about 21 days, and the fetuses were examined at 19 days, these results may have implications for premature human babies, she added.
“The unexpected broadness and specificity of responsiveness of the SCN cells to maternal signals stresses the importance of a healthy maternal circadian system during pregnancy, and points at the potential impact of the absence of such signals in prematurely delivered children.”
Sumová adds, “Our study reveals that distinct maternal signals rhythmically control a variety of neuronal processes in the fetal rat suprachiasmatic nuclei before they begin to operate as the central circadian clock. The results indicate the importance of a well-functioning maternal biological clock in providing rhythmic environment during the fetal brain development.”
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Author: Claire Turner Source: PLOS Contact: Claire Turner – PLOS Image: The image is credited to Alena Sumová and Martin Sládek
Early rhythmicity in the fetal suprachiasmatic nuclei in response to maternal signals detected by omics approach
The suprachiasmatic nuclei (SCN) of the hypothalamus harbor the central clock of the circadian system, which gradually matures during the perinatal period.
In this study, time-resolved transcriptomic and proteomic approaches were used to describe fetal SCN tissue-level rhythms before rhythms in clock gene expression develop.
Pregnant rats were maintained in constant darkness and had intact SCN, or their SCN were lesioned and behavioral rhythm was imposed by temporal restriction of food availability.
Model-selecting tools dryR and CompareRhythms identified sets of genes in the fetal SCN that were rhythmic in the absence of the fetal canonical clock. Subsets of rhythmically expressed genes were assigned to groups of fetuses from mothers with either intact or lesioned SCN, or both groups.
Enrichment analysis for GO terms and signaling pathways revealed that neurodevelopment and cell-to-cell signaling were significantly enriched within the subsets of genes that were rhythmic in response to distinct maternal signals.
The findings discovered a previously unexpected breadth of rhythmicity in the fetal SCN at a developmental stage when the canonical clock has not yet developed at the tissue level and thus likely represents responses to rhythmic maternal signals.