Maternal Control of the Fetal and Neonatal Rat Suprachiasmatic Nucleus

Abstract

The molecular clockwork underlying the generation of circadian rhythmicity within the suprachiasmatic nucleus (SCN) develops gradually during ontogenesis. The authors' previous work has shown that rhythms in clock gene expression in the rat SCN are not detectable at embryonic day (E) 19, start to form at E20 and develop further via increasing amplitude until postnatal day (P) 10. The aim of the present work was to elucidate whether and how swiftly the immature fetal and neonatal molecular SCN clocks can be reset by maternal cues. Pregnant rats maintained under a light-dark (LD) regimen with 12 h of light and 12 h of darkness were exposed to a 6-h delay of the dark period and released into constant darkness at different stages of the fetal SCN development. Adult rats maintained under the same LD regimen were exposed to an identical shifting procedure. Daily rhythms in spontaneous c-fos, Avp, Per1, and Per2 expression were examined within the adult and newborn SCN by in situ hybridization. Exposure of adult rats to the shifting procedure induced a significant phase delay of locomotor activity within 3 days after the phase shift as well as a delay in the rhythms of c-fos and Avp expression within 3 days and Per1 and Per2 expression within 5 days. Exposure of pregnant rats to the shifting procedure at E18, but not at E20, delayed the rhythm in c-fos and Avp expression in the SCN of newborn pups at P0-1. The shifting procedure at E20 did, however, induce a phase delay of Per1 and Per2 expression rhythms at P3 and P6. Hence, 5 days were necessary for phase-shifting the pups' SCN clock by maternal cues, be it the interval between E18 and P0-1 or the interval between E20 and P3, while only 3 days were necessary for phase-shifting the maternal SCN by photic cues. These results demonstrate that the SCN clock is capable of significant phase shifts at fetal developmental stages when no or very faint molecular oscillations can be detected.

Dependence of nighttime sleep duration in one-month-old infants on alterations in natural and artificial photoperiod

“…Nighttime melatonin levels in pregnant women increase after 24 weeks of gestation and reach their maximum level at term2021, suggesting that foetuses are exposed to a relatively high level of melatonin during the final weeks of gestation. Maternal exposure to an alternating photoperiodic environment changes the rhythmic expression of foetal clock genes via melatonin receptors in the foetal SCN, and this expression can be reversed when daily melatonin injections are given to the mother222324. Thus, maternal melatonin is likely to provide photoperiodic information to the foetus, and, hence, the foetal circadian system may be sensitive to changes in extra-uterine environments.…”

Relationship Between Infant and Mother Circadian Rest-Activity Rhythm Pre- and Postpartum, in Comparison to an Infant With Free-Running Rhythm

“…The time course of entrainment for animal circadian rhythm development, which has been represented in a schematic diagram, lists maternal entrainment first, maturation of the retinohypothalamic tract (RHT) second, and finally photic entrainment (Duncan et al, 1986). However, the SCN oscillation mechanism for light in baboons has been identified at a stage equivalent to 25 wks of gestation in the human fetus (Hao & Rivkees, 1999), and molecular studies suggest that maternal entrainment factors affect the circadian system for fetalto-neonatal rats depending on developmental stage (El-Hennamy et al, 2008;Ohta et al, 2002). Thus, it appears that the development of the circadian rhythm in SCN oscillations, including RHT, maternal entrainment, and photic entrainment, does not follow a simple time course as pointed out by Duncan et al (1986).…”

“…However, it is unclear why an infant might have a free-running rhythm after birth. Many animal, but not human, studies have been conducted (Duncan et al, 1986;El-Hennamy et al, 2008;Hao & Rivkees, 1999;Ohta et al, 2002;Reppert & Schwartz, 1983). The site of the master circadian clock is well known to be located in the hypothalamic suprachiasmatic nuclei (SCN), and maternal factors affecting fetal circadian entrainment are thought to be strong, because the maternal circadian system coordinates the phase of the fetal circadian clock (Reppert & Schwartz, 1983).…”

Differential Expression of the Circadian Clock in Maternal and Embryonic Tissues of Mice

“…In rats and hamsters, however, in situ hybridization failed to detect prenatal rhythms [32], [33], [34]. Other studies suggest that molecular rhythms are entrained by maternal rhythms just before birth even if the rhythms are difficult to measure until after birth [35], [36], [37], [38]. In transgenic rats with a luciferase reporter driven by the per1 promoter, fetal SCN and liver cultured a day before birth expressed rhythms that appeared to be influenced by the timing of the mother's feeding schedule during gestation, suggesting the presence of active and entrainable CRCs in those tissues before birth.…”