Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2013

Maternal adaptation to pregnancy: changes in circadian expression of hepatic clock genes during mouse gestation (#182)

Michaela D Wharfe 1 , Peter J Mark 1 , Caitlin S Wyrwoll 1 , Brendan J Waddell 1
  1. School of Anatomy, Physiology & Human Biology, The University of Western Australia, Nedlands, WA, Australia

During pregnancy, maternal physiology is dramatically altered to ensure growth and development of the fetus and placenta whilst maintaining maternal wellbeing. Under normal conditions, clock genes (e.g. Clock, Bmal1, Per1) expressed within the suprachiasmatic nucleus and peripheral tissues (liver, kidney etc), drive the majority of these physiological processes in a circadian manner. We have previously reported that clock gene expression in the maternal liver is altered over days 21-22 of rat pregnancy, presumably as part of maternal adaptation to pregnancy. Here we examined hepatic clock gene expression across gestation in the mouse. C57Bl/6J mice were mated and tissues were collected at day 10-11 or day 18-19 of gestation (term = day 19) at 6 circadian time points (0800, 1200, 1600, 2000, 0000, 0400h) throughout the 24 h period. Robust circadian rhythms in mRNA expression were evident for both Per1 (P<0.001) and Bmal1 (P<0.001) in maternal liver. At day 10 of gestation, Per1 expression increased 25-fold from trough to peak, whereas at day 18 this increase was only 3-fold. Bmal1 expression increased 12-fold (trough to peak) at day 10 and 24-fold at day 18. The expected anti-phase relationship between these two canonical clock genes was observed; Per1 reached peak expression at 2000h coincident with the Bmal1 trough. Absolute expression levels of both Per1 and Bmal1 also decreased between days 10 and 18, with Per1 lower at 2000h (89%; P=0.002; t-test), 0000h (62%; P=0.002) and 0400h (42%; p=0.009). Bmal1 expression was similarly reduced at each circadian time point (up to 96%; P<0.001; t-test). Overall, our data indicate that major adaptations in the core circadian clock machinery occur in the maternal liver from mid to late pregnancy in the mouse.