Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice

Abstract

Modern life involves chronic circadian disruption through artificial light and these disruptions are associated with numerous mental and physical health maladies. Because the developing nervous system is particularly vulnerable to perturbation, we hypothesized that early-life circadian disruption would negatively impact offspring development and adult function. Pregnant mice were subjected to chronic circadian disruption from the time of uterine implantation through weaning. To dissociate in utero from postnatal effects, a subset of litters was cross-fostered at birth from disrupted dams to control dams and vice versa. Postnatal circadian disruption was associated with reduced adult body mass, social avoidance, and hyperactivity. In utero disruption resulted in more pronounced social avoidance and hyperactivity, phenotypes not abrogated by cross-fostering to control mothers. To examine whether circadian disruption affects development by acting as an early life stressor, we examined birthweight, litter size, maternal cannibalism, and epigenetic modifications. None of these variables differed between control and disrupted dams, or resembled patterns seen following early-life stress. Our findings indicate that developmental chronic circadian disruption permanently affects somatic and behavioral development in a stage-of-life-dependent manner, independent of early life stress mechanisms, underscoring the importance of temporal structure during development, both in utero and early postnatal life.

Light and Circadian Signaling Pathway in Pregnancy: Programming of Adult Health and Disease

“…Given that only a few human studies are available on this issue and that these observational studies cannot directly establish a causal relationship between maternal chronodisruption and lifelong health in the offspring, animal models are of great importance to identify which mechanisms underlying maternal circadian disruption may influence the programming of offspring phenotypes and lead to the development of specific preventive interventions. Table 1 summarizes various animal models utilized to investigate the relationship between maternal circadian rhythm disruption and offspring health [56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74]. Of note is that not only constant light, but also diurnal light deficiency and/or continuous darkness, are disruptive for the circadian system.…”

“…Chronic phase shifts of the photoperiod throughout pregnancy programs adult offspring to display impaired endocrine, cardiovascular, and metabolic function [59,60]. Additionally, CPH during pregnancy has been reported to induce behavior changes characterized as hyperactivity and social avoidance in young adult rats [61]. Furthermore, gestational CPH has been reported to disrupt the peripheral liver clock [62].…”

“…The associations between maternal chronodisruption and the risks for many adult diseases are illustrated in Figure 2. Induced hyperinsulinemia and insulin intolerance in 12-month-old female rat offspring [59] Altered endocrine, cardiovascular, and metabolic function in 90-day-old rat offspring [60] Induced behavior changes with hyperactivity and social avoidance in 60-day-old rat offspring [61] Disrupted daily rhythms in hepatic clock genes in 3-month-old rat offspring [62] Pinealectomy Surgical removal of pineal gland…”

Association of Iron Status and Intake During Pregnancy with Neuropsychological Outcomes in Children Aged 7 Years: The Prospective Birth Cohort Infancia y Medio Ambiente (INMA) Study

“…Epidemiological studies have demonstrated that optimizing brain development in early life has been associated with long-term consequences for individuals, for instance, academic performance, the level of education attained [1][2][3], and mental well-being in adulthood [4]. In particular, early-life environmental factors such as smoking, healthy lifestyle, and other factors have been suggested to play a major role in neurodevelopmental processes [5][6][7][8][9][10][11]. Accordingly, some previous studies have evidenced a relationship between suboptimal maternal diet in pregnancy and poorer mental and psychomotor development in offspring [5,6,[12][13][14][15][16].…”

Epigenome-wide association study of placental DNA methylation and maternal exposure to night shift work in the Rhode Island Child Health Study

“…Animal studies suggest circadian disruption in utero negatively affects the health and development of offspring 8 . Mice exposed to a 22-hour light-dark cycle, instead of the normal 24-hour cycle, had altered methylation patterns in the SCN and altered circadian behavior; differential methylation was also found for genes related to axonal migration, synaptogenesis, and neuroendocrine hormones 9 .…”