B A O'Connell1, K M Moritz, D W Walker, H Dickinson. 1. The Ritchie Centre, Monash Institute of Medical Research, Monash University, 27-31 Wright St, Clayton, Victoria 3800, Australia.
Abstract
INTRODUCTION: Elevated maternal glucocorticoids during human pregnancy suppress fetal growth, more so if the fetus is male. The synthetic glucocorticoid dexamethasone (DEX) is known to affect placental glucose transport, but whether this also affects placental glycogen stores has not been investigated. METHOD: We examined the short and long term consequences of a single, 60 h exposure to DEX at mid gestation on the glycogen pathway in the placenta of the spiny mouse, with a focus on identifying sex-dependent differences in expression of genes involved in glycogen cell formation (PCDH12), and regulation of glycogen synthesis (GSK3B, GYS1, GBE1, FOXO1, UGP2). RESULTS: Placentas from female fetuses had increased amounts of glycogen on day 25 of gestation (term is 39 days) as identified by positive Periodic acid Schiff (PAS) reaction staining. DEX administration initially reduced expression of GSK3B, GYS1, GBE1, FOXO1, UGP2 in both male and female placentas, but reduced histologically detectable glycogen storage in placentas of female fetuses only. The DEX-induced reduction in expression of GSK3B and UGP2 persisted until day 37 of gestation, an effect that was significantly greater in the male placenta. DISCUSSION/ CONCLUSION: We conclude that constitutive placental glycogen storage is regulated in pregnancy in a sex-dependant manner, and that glucocorticoids such as DEX induce sex-dependent changes in glycogen storage. Placental glycogen metabolism and its response to glucocorticoids may contribute to the different sensitivities of male and female fetuses to the effects of maternal illness and stress in utero. Crown
INTRODUCTION: Elevated maternal glucocorticoids during human pregnancy suppress fetal growth, more so if the fetus is male. The synthetic glucocorticoid dexamethasone (DEX) is known to affect placental glucose transport, but whether this also affects placental glycogen stores has not been investigated. METHOD: We examined the short and long term consequences of a single, 60 h exposure to DEX at mid gestation on the glycogen pathway in the placenta of the spiny mouse, with a focus on identifying sex-dependent differences in expression of genes involved in glycogen cell formation (PCDH12), and regulation of glycogen synthesis (GSK3B, GYS1, GBE1, FOXO1, UGP2). RESULTS: Placentas from female fetuses had increased amounts of glycogen on day 25 of gestation (term is 39 days) as identified by positive Periodic acid Schiff (PAS) reaction staining. DEX administration initially reduced expression of GSK3B, GYS1, GBE1, FOXO1, UGP2 in both male and female placentas, but reduced histologically detectable glycogen storage in placentas of female fetuses only. The DEX-induced reduction in expression of GSK3B and UGP2 persisted until day 37 of gestation, an effect that was significantly greater in the male placenta. DISCUSSION/ CONCLUSION: We conclude that constitutive placental glycogen storage is regulated in pregnancy in a sex-dependant manner, and that glucocorticoids such as DEX induce sex-dependent changes in glycogen storage. Placental glycogen metabolism and its response to glucocorticoids may contribute to the different sensitivities of male and female fetuses to the effects of maternal illness and stress in utero. Crown