Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Maternal corticosterone exposure has sex specific effects on the renal stress response. (#27)

James SM Cuffe 1 , Danielle Burgess 1 , Karen M Moritz 1
  1. The University of Queensland, St Lucia, QLD, Australia

Maternal exposure to the stress hormone corticosterone during pregnancy can impair fetal kidney development and program sex specific disease in offspring. Outcomes are largely regulated by placental metabolism of corticosterone by the enzyme HSD11B2, which itself is regulated by corticosterone in a sex specific manner.  HSD11B2 is also expressed in the fetal and adult kidney where it metabolises excess corticosterone to prevent over activation of the glucocorticoid (GR) and mineralocorticoid (MR) receptors which are important regulators of kidney development and renal function. The effects of maternal corticosterone exposure on this renal stress system in the fetus and in offspring are relatively unknown but may play a role in the programming of long term disease.

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 kidneys collected for analysis of MR, GR and HSD11B2 mRNA levels. Additional mice littered down and offspring kidneys were collected at 6 months for assessment of mRNA and protein levels of MR, GR and HSD11B2.

Maternal corticosterone exposure increased renal mRNA levels of MR, GR and HSD11B2 in male but not female E14.5 fetuses. Similarly, maternal corticosterone exposure increased the mRNA levels of MR and GR and increased mRNA and protein levels of HSD11B2 in the kidneys of 6 month old male but not female offspring.

This study demonstrates that kidneys of male and female fetuses have different renal responses to a maternal stress challenge. This indicates that fetal corticosterone exposure is sex specific and that kidneys of male fetuses may be at an increased risk of glucocorticoid associated renal deficits.  Additionally, this male specific renal stress response persists into adulthood where it may contribute to the sex specific renal health deficits observed in offspring.