Getting off beat: Circadian rhythm changes during pregnancy (#170)
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 behavioural cues. The molecular clock machinery comprises a network of ‘clock’ genes, namely Clock, Bmal1, Period and Cryptochrome. These clock genes generate endogenous oscillations that drive rhythmic expression of downstream genes and thus physiological and behavioural processes. Importantly, disturbances in clock gene expression are implicated in a range of pathologies including cancer and obesity.
Pregnancy is arguably the most physiologically challenging state that an organism encounters across the life cycle. Accordingly, major maternal metabolic adaptations are required to maintain maternal homeostasis whilst concurrently providing for the growing fetus. Interestingly, key changes in hepatic clock gene expression in rodent pregnancy (suppression of Bmal1, Clock and Per rhythms) are generally opposite to those that occur in obesity (amplification of Bmal1, Per and Cry gene rhythms). This suggests that obesity may counter the normal pregnancy-induced changes in hepatic clock gene rhythms and associated changes in downstream genes and thus maternal adaptations.
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. 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.