This paper provides a new and challenging insight into the role of oxytocin in reproduction. Previous studies using oxytocin-deficient mice have shown that birth proceeds without oxytocin. However, this conclusion was surprising since we and others have shown that repeated oxytocin antagonist administration delays the onset of labour and prolongs birth while oxytocin pulse administration advances the onset of labor and accelerates birth (Antonijevic IA et al 1995, Douglas AJ et al 2002). Here the data show that when a circadian shift is imposed in early pregnancy, oxytocin-deficient mice are unable to adapt and the timing of birth becomes randomly scattered. Therefore, this paper reveals that where neuroendocrine systems are challenged, oxytocin emerges as important in determining the timing of onset of birth. So, we can now conclude that brain oxytocin is necessary for birth.

The strengths of this paper are in its insight, finding the right question to ask about whether oxytocin is necessary for birth mechanisms. Evidently oxytocin is not necessary in the periphery for birth to proceed normally, but now we know that when normal brain systems are disrupted during pregnancy they require oxytocin to enable the appropriate adaptations leading to optimal birth. Since the stimulus applied – circadian shift – was initiated in early pregnancy, this should stimulate discussion about how early in pregnancy oxytocin is required for the timing of birth and for adaptation of brain mechanisms that facilitate birth.

The study has some weaknesses too. Circadian peripheral oxytocin secretion is analysed in mid-late pregnancy and does not alter with circadian shift, and this is interpreted as a normal adaptation of the oxytocin system to such stimuli. We might speculate that the circadian oxytocin secretory pattern is affected initially after the circadian shift, in early pregnancy (or indeed in non-pregnant mice), but this is not analysed so it is not known whether or how quickly the oxytocin system normally responds to this change in day length imposed around the time of implantation. In fact we might speculate that even a transient change in the oxytocin secretory pattern would influence implantation (oxytocin is required for the prolactin surges in early pregnancy, McKee et al DT 2007) and trophoblast/placental mechanisms and, so, the placental clock.

Furthermore, it is not clear how circadian shift/timing signals to oxytocin neurones, what the brain mechanisms are, or whether central oxytocin release and action play a role. Oxytocin plays a key role in the brain in mediating behaviours, and one of the key findings in oxytocin or oxytocin receptor null mice is their abnormal social behaviours– if we consider parturition as another reproductive behaviour we might expect central oxytocin to be important in birth too. However, this paper does not consider how oxytocin in the brain is contributing to the intriguing behavioural shift after circadian shift. It seems that we have been given another peek into the already complex role of oxytocin in brain function, but many new questions arise about its underlying mechanisms and how it relates to normal perinatal physiology.