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 SCN that synchronises peripheral clocks (e.g. liver and adipose) via endocrine, autonomic and behavioural cues. The clock machinery comprises a network of ‘clock’ genes (Clock, Bmal1, Per1-3 and Cry1-2) that generates rhythmic oscillations in physiological and behavioural processes. Importantly, disturbances in clock gene expression are implicated in the etiology of several pathologies including metabolic disturbances (e.g. obesity).
Successful pregnancy requires major metabolic adaptations to maintain maternal homeostasis and provide for the growing fetus. We have identified marked changes in hepatic clock gene expression in rodent pregnancy (e.g. suppression of Bmal1 and Per1 in both rat and mouse) (1). Because these pregnancy changes are opposite to those induced by obesity in non-pregnant rodents, we are exploring whether obesity disturbs normal circadian maternal adaptations to pregnancy. For example, we have observed that maternal obesity suppresses liver expression of Bmal1 but increases that of Per2 and Per3; obesity also reduces maternal core body temperature and alters its pre-partum decline.
Circadian disruptions also compromise placental function and fetal growth, and we have shown that the rat placenta expresses all clock genes in a zone-specific manner (1). Although placental clock genes exhibit some time-of-day variation, the conventional transcriptional-translational feedback loops are less robust and coordinated than in adult tissues. Nevertheless, clear circadian variation is evident for several other placental genes including those encoding nutrient transporters, inflammatory cytokines and the 11B-HSD enzymes (2). Given the relative stability of placental clock gene expression, we hypothesise that rhythmic placental function is driven by maternal signals. How this rhythmic function is influenced by maternal obesity is the focus of our current studies.