Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Maternal corticosterone exposure in the mouse induces placental oxidative stress and dysregulates expression of antioxidant and apoptotic genes in a sex specific manner (#255)

James SM Cuffe 1 , Lucy A Bartho 1 , Karen M Moritz 2 , Tony V Perkins 1
  1. Griffith University, Gold Coast, QUEENSLAND, Australia
  2. The School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia

Introduction: Maternal exposure to the stress hormone corticosterone during pregnancy in mice programs sex specific disease outcomes with overt disease in male offspring. Corticosterone increases placental weight and junctional zone area in placentas of male but not female offspring.  Reactive oxygen species are known to be important regulators of placental development. This study investigated the role of oxidative stress and apoptosis in the sex specific placental deficits caused by maternal corticosterone exposure.


Methods: Pregnant C57/BL/6 mice were surgically implanted with osmotic minipumps primed to release corticosterone (33µg/kg/h for 60h beginning at E12.5) or left untreated. At E14.5, dams were killed and placentas collected for RNA and protein extraction. Placental protein carbonyl levels were measured in protein extracts as an indicator of oxidative stress. The mRNA expression of key antioxidant and apoptosis factors was measured using QPCR (Thioredoxin reductase 1-Trxr1, Trxr2 and Bax).


Results: Maternal corticosterone exposure increased placental protein carbonyl levels in placentas of female but not male fetuses.  Corticosterone exposure increased placental Trxr1 gene expression in female but not male fetuses and reduced Trxr2 levels in males but not females. Placental Bax expression was increased in placentas of female but not male fetuses exposed to Corticosterone.


Conclusion: This study indicates that prenatal corticosterone exposure increases markers of oxidative stress and apoptosis in placentas of female but not male fetuses. Corticosterone increases expression of the cytosolic Trxr1 in females while reducing the mitochondrial Trxr2 in placentas of male fetuses. These findings are of interest considering that male offspring develop overt disease and females are relatively protected. The fact that placentas of female fetuses do not undergo the corticosterone induced increase in placental size may be due to increased apoptosis which allows appropriate placental remodeling, maintenance of optimal placental efficiency thus having protective outcomes for the offspring.