Maternal Feeding Controls Fetal Biological Clock

Abstract

BackgroundIt is widely accepted that circadian physiological rhythms of the fetus are affected by oscillators in the maternal brain that are coupled to the environmental light-dark (LD) cycle.Methodology/Principal FindingsTo study the link between fetal and maternal biological clocks, we investigated the effects of cycles of maternal food availability on the rhythms of Per1 gene expression in the fetal suprachiasmatic nucleus (SCN) and liver using a transgenic rat model whose tissues express luciferase in vitro. Although the maternal SCN remained phase-locked to the LD cycle, maternal restricted feeding phase-advanced the fetal SCN and liver by 5 and 7 hours respectively within the 22-day pregnancy.Conclusions/SignificanceOur results demonstrate that maternal feeding entrains the fetal SCN and liver independently of both the maternal SCN and the LD cycle. This indicates that maternal-feeding signals can be more influential for the fetal SCN and particular organ oscillators than hormonal signals controlled by the maternal SCN, suggesting the importance of a regular maternal feeding schedule for appropriate fetal molecular clockwork during pregnancy.

The Uterus Sustains Stable Biological Clock during Pregnancy

“…1. Previous studies have suggested that the fetus in the uterus uses maternal signals to adapt the fetal biological clock to the maternal environment (Reppert and Schwartz 1983;Davis and Gorski 1988;Parraguez et al 1996;Kennaway 2002;Ohta et al 2002Ohta et al , 2003Ohta et al , 2008Sládek et al 2004;Li and Davis 2005;Saxena et al 2007). These signals are considered to be a variety of nonphotic stimuli including circadian fluctuations in hormonal and nutritional signals from the mother, placental filtering of those signals, and uterine motility (Serón-Ferré et al 2007).…”

“…Photon counts from each culture were detrended with a 2-h running average as described previously (Yamazaki et al 2000) with modifications using exmax software (gift from Mr. Tuyoshi Yaita and Dr. Shigenobu Shibata, Waseda University, Tokyo, Japan) (Hayasaka et al 2007;Ohta et al 2008;Hirao et al 2009). The period of Per1-luc activity (recorded from 12 to 84 h in vitro) was assessed for each SCN culture and calculated by averaging the period between the first and second peaks and the period between the second and third peaks as previously described (Yamazaki et al 2000;Ohta et al 2005).…”

“…Among them the suprachiasmatic nuclei (SCN) of the anterior hypothalamus function as the master pacemaker at the top of the hierarchy, and coordinate clocks in peripheral organs such as the heart, lung, liver, kidney, pancreas and non-pregnant uterus (Hastings et al 2003;Dolatshad et al 2006;Maywood et al 2007). During pregnancy, the fetus itself functions as an organ oscillator in the mother and uses maternal signals to adjust the fetal biological clock to the extrauterine environment (Serón-Ferré et al 2007;Ohta et al 2008).…”

“…The intrauterine environment is suggested to be a circadian environment in which fetuses are subject to a variety of nonphotic stimuli, including circadian fluctuations in hormonal and nutritional signals from the mother, placental filtering of those signals, and uterine motility (Serón-Ferré et al 2007;Ohta et al 2008). In mammals, maternal melatonin has a circadian pattern in its plasma concentration and is thought to convey information on the light-dark cycle to the fetus, thereby synchronizing the developing fetus's biologic clock to the 24-hour cycle (Davis and Mannion 1988;Illnerová et al 1993;Serón-Ferré et al 2007).…”

“…In mammals, maternal melatonin has a circadian pattern in its plasma concentration and is thought to convey information on the light-dark cycle to the fetus, thereby synchronizing the developing fetus's biologic clock to the 24-hour cycle (Davis and Mannion 1988;Illnerová et al 1993;Serón-Ferré et al 2007). Fetal biological clock has also been reported to be influenced by the maternal feeding schedule during pregnancy (Weaver and Reppert 1986;Ohta et al 2008). The circadian molecular properties of the pregnant uterus and placenta, however, have not been fully examined in spite of the importance of understanding their circadian effects on fetal physiology.…”