Maternal glucocorticoid exposure alters placental expression of the renin-angiotensin system — ASN Events

Maternal glucocorticoid exposure alters placental expression of the renin-angiotensin system (#73)

James SM Cuffe 1 , Hayley Dickinson 2 , David G Simmons 1 , Lee O'Sullivan 1 , Karen M Moritz 1
  1. University of Queensland, St Lucia, Qld, Australia
  2. Monash University, Melbourne, Australia

Introduction: The renin angiotensin system (RAS) is known to be involved in the development of fetal organs. It has been implicated in placental development and is associated with disorders related to the placenta such as preeclampsia. Excess maternal glucocorticoid (GC) exposure is known to disrupt placental development and impair fetal growth in a sexually dimorphic manner. This study investigates the effects of maternal dexamethasone exposure on the RAS in the placenta.
Methods: Osmotic minipumps containing either saline or Dexamethasone (Dex-1µg/kg/h) were implanted into pregnant mice at E12.5 and primed to release their contents for 60h. Animals were killed at E14.5 and E17.5 and placentas from male and female fetuses collected. The mRNA levels of Ace1, Ace2, the angiotensin receptors (AT1a, AT1b, AT2, Mas-1), pro-renin receptor (PPR), renin and angiotensinogen were examined via qPCR and in situ hybridisation.
Results: At 14.5 placental weight was less in the Dex group but only in those from female fetuses. Dex increased PRR expression at E14.5 in placentas of both sexes. At 17.5, placental weights in treatment groups were similar. Expression of the AT1a and AT1b receptors were reduced at 17.5 in placentas from female fetuses exposed to Dex whilst the expression of Ace1, Ace2, Agt and Mas receptor were unchanged at either age. Renin and the AT2 receptor were undetected or lowly expressed in the placenta at both ages. AT1 receptors were localised to the labyrinth in endothelial cells lining blood spaces.
Conclusion: This data shows that, similar to our findings on gene expression of placental growth and vasculogenesis factors (1), maternal Dex exposure can affect the expression of the placental RAS in a sex specific manner. Placentas of females showed significant alterations in gene expression whilst placentas of males remained largely unchanged.

  1. Cuffe et al, Placenta 32:981-989, 2011.