Maternal eating behavior is a major synchronizer of fetal and postnatal peripheral clocks in mice

Abstract

Most living organisms show circadian rhythms in physiology and behavior. These oscillations are generated by endogenous circadian clocks, present in virtually all cells where they control key biological processes. To study peripheral clocks in vivo, we developed an original model, the Rev-Luc mouse to follow noninvasively and longitudinally Rev-Luc oscillations in peripheral clocks using in vivo bioluminescence imaging. We found in vitro and in vivo a robust diurnal rhythm of Rev-Luc, mainly in liver, intestine, kidney and adipose tissues. We further confirmed in vivo that Rev-Luc peripheral tissues are food-entrainable oscillators, not affected by age or sex. These data strongly support the relevance of the Rev-Luc model for circadian studies, especially to investigate in vivo the establishment and the entrainment of the rhythm throughout ontogenesis. We then showed that Rev-Luc expression develops dynamically and gradually, both in amplitude and in phase, during fetal and postnatal development. We also demonstrate for the first time that the immature peripheral circadian system of offspring in utero is mainly entrained by maternal cues from feeding regimen. The prenatal entrainment will also differentially determine the Rev-Luc expression in pups before weaning underlining the importance of the maternal chrononutrition on the circadian system entrainment of the offspring.

Simulated shift work disrupts maternal circadian rhythms and metabolism, and increases gestation length in sheep

“…In rodents, rhythmic clock gene mRNA expression is detectable in fetal tissues by the end of gestation (Canaple et al . ). Interestingly, these fetal clocks are sensitive to the external environment and their timing alters in response to maternal photoperiod shifts or constant light (Torres‐Farfan et al .…”

“…Altered skeletal muscle rhythms are probably reflected in other peripheral clocks, possibly including those of the developing fetus. In rodents, rhythmic clock gene mRNA expression is detectable in fetal tissues by the end of gestation (Canaple et al 2018). Interestingly, these fetal clocks are sensitive to A and B) and insulin (C and D) concentrations following I.V.…”

“…These altered maternal metabolic profiles are expected to be mirrored in the fetal circulation (Simonetta et al 1991) and to affect fetal ACTH and cortisol profiles (Simonetta et al 1991). Studies in mice and rats have shown that feeding is a key zeitgeber for the fetus, whereas restricting maternal food availability to the light period (reversing normal timing of rodent feeding activity) inverts the rhythms of fetal clock gene expression (Canaple et al 2018). Taken together, this suggests that changes in the maternal circadian timing system induced by SSW exposure probably influence fetal behavioural, endocrine and molecular rhythms.…”

Maternal-Fetal Circadian Communication During Pregnancy

“…Finally, hormonal rhythms are not the only possible entraining signals. Maternal feeding can act as an entraining signal in certain circumstances (16,85,86). For example, offspring from SCNlesioned dams drank at random times of the day relative to each other, but showed inter-and intra-litter synchronization following 4-h restricted daily feeding during pregnancy (16).…”

Gestational jet lag predisposes to later-life skeletal and cardiac disease

“…Repeated jet lag causes the circadian clock of the pregnant mouse to continuously adjust, affecting food intake and metabolism. Maternal control of the fetal clock occurs via metabolic cues and is therefore likely affected by the repeated jet lag (Canaple et al 2018;Ohta et al 2008), which accordingly could impinge on the development of the circadian system. Starting at the age of 12 weeks, the circadian behavior of the male offspring was assessed by monitoring voluntary wheel running activity under various light conditions (representative actograms are shown in Figure S1D).…”