Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Changes in circadian expression of hepatic and adiposal clock genes during maternal adaptation to pregnancy in the mouse (#347)

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. Many physiological processes e.g. glucose homeostasis and oxidative metabolism, oscillate in circadian patterns entrained to the light-dark cycle. Clock genes (e.g. Clock, Bmal1, Per1) within the suprachiasmatic nucleus and peripheral tissues (liver, kidney etc.), drive these rhythmic metabolic processes. How metabolic adaptation to pregnancy impacts on peripheral clock gene expression is currently unclear. Here we examined hepatic and intraperitoneal adiposal adaptations in clock gene expression across gestation in the mouse. Tissues were collected from C57Bl/6J mice (n=7-8 per group) in non-pregnant animals, and on days 6, 10, 14 or 18 of gestation (term=19 days). Collections were performed at 0800, 1200, 1600, 2000, 0000, 0400 h across each day. mRNA expression for several clock genes was measured by RT-qPCR.

 Robust circadian rhythms were evident for Bmal1 expression (P<0.001) in both the maternal liver and adipose tissue at all stages. Pregnancy-induced changes in Bmal1 expression were more pronounced in liver than in adipose tissue. Peak hepatic Bmal1 expression was highest at day 6 of gestation, after which peak levels markedly declined towards term with peak expression 75% lower at day 18 than at day 6 (P<0.001). These changes reduced the amplitude of hepatic Bmal1 rhythm near term. In contrast, peak adiposal Bmal1 expression showed very little change across pregnancy, however, trough adiposal Bmal1 expression (between 1600 and 2000) increased towards term with a 2.4-fold increase in expression from day 6 to day 18 (P=0.038).

 Overall, our data indicate that major adaptations in the core circadian clock machinery occur in the liver throughout pregnancy in the mouse whereas changes in expression within adipose tissue are more subtle. Hepatic changes in rhythmicity may alter substrate supply to the developing fetus as gestation progresses.