Oral Presentation 6th Australian Health and Medical Research Congress 2012

Treatment of pregnant spiny mice at mid-gestation with a synthetic glucocorticoid has sex-dependent effects on placental glycogen stores (#61)

Bree A O'Connell 1 , Karen M Moritz 2 , David W Walker 1 , Hayley Dickinson 1
  1. Monash Institute of Medical Research, Clayton, VIC, Australia
  2. School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia

Introduction: High maternal levels of glucocorticoids during pregnancy are associated with increased rates of preterm birth and stillbirth; with higher incidences of these occurring if the fetus is male. A primary role of the placenta is to maintain optimal glucose supply to the feto-placental unit. Glucose can be transferred directly to the fetus and/or stored in specialised glycogen-containing cells in the placenta. Excess glucocorticoids affect placental glucose transfer in a sexually dimorphic and time-dependant manner, but their effect on the deposition of glycogen in the placenta is unknown.

Aim: To describe the placental glycogen cell population in the spiny mouse and examine the consequences of a brief mid-gestation glucocorticoid pulse on the placental glycogen pathway, focusing on identifying differences between males and females.

Method: Pregnant spiny mice were either killed at 5-daily intervals between 15 days gestation (dGA) and term (39dGA); or treated with DEX or saline for 60h at mid-gestation and tissues collected 3-days and 2-weeks thereafter. Placental glycogen was analysed by Periodic Acid Schiff (PAS) histochemistry and qPCR within the placental spongy zone region.

Results: Expression of genes involved in glycogen cell formation (GJB3) and regulation of glycogen synthesis (GSK3B, GBE1) were sexually dimorphic throughout gestation. Placentas from female fetuses had increased histological glycogen deposition at 25dGA compared to males. DEX administration reduced the mRNA expression of glycogen regulators (GSK3B, GYS1, GBE1, FOXO1, UGP2) in both sexes, but reduced histological glycogen in placentas of female fetuses only. Expression of GSK3B and UGP2 remained suppressed two-weeks post-DEX administration in placentas from both sexes.

Conclusion: Males and females appear to differ in placental glycogen storage and metabolism during development and after brief exposure to glucocorticoids. Our findings raise the question, do differences in placental glycogen storage/metabolism between the sexes account for the greater risk of mortality for the male conceptus?