Characterising the dynamics of placental glycogen stores in the mouse

Abstract

Introduction: The placenta performs a range of functions to support fetal growth. In addition to facilitating nutrient transport, the placenta also stores glucose as glycogen, which is thought to maintain fetal glucose supply during late gestation. However, evidence to support such a role is currently lacking. Similarly, our understanding of the dynamics of placental glycogen metabolism in normal mouse pregnancy is limited.

Methods: We quantified the placental glycogen content of wild type C57BL/6JOlaHsd mouse placentas from mid (E12.5) to late (E18.5) gestation, alongside characterising the temporal expression pattern of genes encoding glycogenesis and glycogenolysis pathway enzymes. To assess the potential of the placenta to produce glucose, we investigated the spatiotemporal expression of glucose 6-phosphatase by qPCR and in situ hybridisation. Separate analyses were undertaken for placentas of male and female conceptuses to account for potential sexual dimorphism.

Results: Placental glycogen stores peak at E15.5, having increased over 5-fold from E12.5, before declining by a similar extent by E18.5. Glycogen stores were 17% higher in male placentas than in females at E15.5. Expression of glycogen branching enzyme (Gbe1) was reduced ~40% towards term. Expression of the glucose 6-phosphatase isoform G6pc3 was enriched in glycogen trophoblast cells and increased towards term.

Discussion: Reduced expression of Gbe1 suggests a decline in glycogen branching towards term. Expression of G6pc3 by glycogen trophoblasts is consistent with an ability to produce and release glucose from glycogen stores. However, the ultimate destination of the glucose generated from placental glycogen remains to be elucidated.

Keywords: G6pc3; Glucose 6-phosphatase; Glycogen cells; Mouse placenta; Placental glycogen.