Suppression of the intrarenal renin-angiotensin system may contribute to a nephron deficit following short-term maternal corticosterone administration (#352)
Introduction: Synthetic glucocorticoids (GC) administration to women threatening preterm labour has increased survival of premature infants. While life-saving, synthetic GCs have detrimental effects on the developing kidney. This study investigated whether elevations in maternal endogenous GC (corticosterone, CORT) as would be expected during periods of stress, alters the intra-renal expression of components of the renin-angiotensin system (RAS), a vital regulator of kidney development and whether these alterations would inturn impact upon kidney structure.
Methods: C57/Bl6 mice (N=16) received CORT (33µl/kg/h) via an osmotic mini pump from embryonic (E) day 12.5-14.5. Controls remained untreated (UNTR, N=16). A subset of dams (N=7 per group) were culled at E17.5 and kidneys excised from male and female embryos for determination of expression of components of RAS via qRT-PCR. The remaining animals littered-down naturally and growth of the offspring was monitored from postnatal day (P) 2-30. A subset offspring from both sexes were culled at P30 and kidneys excised to determine nephron number.
Results: Prenatal CORT treatment had no effect on body weights at P2 and P30. CORT administration significantly reduced expression of angiotensinogen, angiotensin converting enzyme-2 (ACE-2), angiotensin II receptors type 1a, 1b, 2 and mas-1 proto-oncogene in both male and female embryonic kidneys. Renin and ACE were only reduced in CORT treated male kidneys. Maternally CORT treated male offspring had a 35% decrease in nephron number compared to UNTR males at P30 (P<0.01).
Conclusion: Maternal CORT overexposure very early in development caused a significant reduction in expression of vital components of the RAS involved in kidney development. Despite CORT being administered for only 60 hours, the reduction in nephron number at P30 indicates that the effects of this short-term CORT exposure on the fetal kidney are permanent. We are currently investigating if this nephron deficit results in compromised renal function in adult offspring.