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

Abstract

Light is a crucial environmental signal that affects elements of human health, including the entrainment of circadian rhythms. A suboptimal environment during pregnancy can increase the risk of offspring developing a wide range of chronic diseases in later life. Circadian rhythm disruption in pregnant women may have deleterious consequences for their progeny. In the modern world, maternal chronodisruption can be caused by shift work, jet travel across time zones, mistimed eating, and excessive artificial light exposure at night. However, the impact of maternal chronodisruption on the developmental programming of various chronic diseases remains largely unknown. In this review, we outline the impact of light, the circadian clock, and circadian signaling pathways in pregnancy and fetal development. Additionally, we show how to induce maternal chronodisruption in animal models, examine emerging research demonstrating long-term negative implications for offspring health following maternal chronodisruption, and summarize current evidence related to light and circadian signaling pathway targeted therapies in pregnancy to prevent the development of chronic diseases in offspring.

Keywords: circadian rhythm; developmental origins of health and disease (DOHaD); developmental programming; glucocorticoid; hypertension; light; melatonin; pregnancy.

Figure 1

Schema outlining the light and circadian signaling pathway in pregnancy. The retinohypothalamic tract transmits light from the eyes to the suprachiasmatic nucleus (SCN). In the pineal gland, melatonin synthesis follows a rhythm driven by the SCN. Melatonin has pleiotropic biological function whereby it regulates pregnancy and fetal development. The SCN also stimulates the release of glucocorticoids (GCs) in the adrenal gland in a light-dependent manner. GC signaling is crucial for fetal development. The circadian clock system consists of central and peripheral clocks, which are coordinated to produce daily rhythms. The molecular mechanisms responsible for the generation of the rhythmicity within the SCN and peripheral clocks are regulated by interactive transcriptional–translational feedback loops between the clock genes, including Per1, Per1, Cry1, Cry2, CLOCK, BMAL1, Rev-erbα, and CK1ε, and their protein products. The cellular circadian clock consists of positive and negative interlinked regulatory limbs. CLOCK and BMAL1 form a heterodimer that positively activates the rhythmic expression of Per, Cry, and Rev-erbα genes. The negative limb includes the PER and CRY proteins. After nuclear translocation of both proteins, the PER:CRY complex interacts with the CLOCK:BMAL1 heterodimer and inhibits CLOCK:BMAL1-mediated transcription. The regulation of Bmal1 transcription is mediated mostly by REV-ERBα. The SCN and peripheral clocks operate with similar components and share a similar molecular core clock mechanism. Circadian signals can transfer from mother to fetus. The rhythms of melatonin and GCs provide synchronization signals for peripheral clocks. The interactions between light, the circadian clock, and the circadian signals melatonin and GCs in pregnancy ultimately impact the health of the mother and offspring.

Figure 2

Schematic illustration of the association between maternal chronodisruction, fetal programming, and increased vulnerability to many adult disease.