A rhythmic placenta? Circadian variation, clock genes and placental function

Abstract

Physiological rhythms entrained by the circadian clock are present in virtually all organs including those of the reproductive system. In mammals, circadian timing is driven by a 'master clock' in the suprachiasmatic nucleus that influences peripheral tissue clocks via endocrine, autonomic and behavioral cues. The molecular clock machinery comprises a network of 'clock' genes, namely Clock, Bmal1, Per1, Per2, Per3, Cry1 and Cry2. These clock genes generate endogenous oscillations that drive rhythmic expression of downstream genes and thus physiological and behavioral processes. Importantly, disturbances in clock gene expression are implicated in a range of pathologies including cancer and obesity. The recent recognition that clock genes are expressed in the placenta, together with observations linking circadian disruption with compromised placental function, suggests that circadian variation may be an important component of the normal placental phenotype. In this review we consider this possibility in the context of maternal circadian physiology in pregnancy. While there is good evidence for rhythmic expression of several genes in the rodent placenta, the conventional transcriptional-translational feedback loops of the clock machinery appear less robust and coordinated. Further study is needed to elucidate the function of the placental clock genes across gestation and among different species, particularly those in which greater circadian development occurs in utero. Such studies will likely provide important insights into placental physiology and pathology.