Abstract
Short‐term maternal corticosterone (Cort) administration at mid‐gestation in the mouse reduces nephron number in both sexes while programming renal and cardiovascular dysfunction in 12‐month male but not female offspring. The renal renin–angiotensin–aldosterone system (RAAS), functions in a sexually dimorphic manner to regulate both renal and cardiovascular physiology. This study aimed to identify if there are sex‐specific differences in basal levels of the intrarenal RAAS and to determine the impact of maternal Cort exposure on the RAAS in male and female offspring at 6 months of age. While intrarenal renin concentrations were higher in untreated females compared to untreated males, renal angiotensin II concentrations were higher in males than females. Furthermore, basal plasma aldosterone concentrations were greater in females than males. Cort exposed male but not female offspring had reduced water intake and urine excretion. Cort exposure increased renal renin concentrations and elevated mRNA expression of Ren1, Ace2, and Mas1 in male but not female offspring. In addition, male Cort exposed offspring had increased expression of the aldosterone receptor, Nr3c2 and renal sodium transporters. In contrast, Cort exposure increased Agtr1a mRNA levels in female offspring only. This study demonstrates that maternal Cort exposure alters key regulators of renal function in a sex‐specific manner at 6 months of life. These finding likely contribute to the disease outcomes in male but not female offspring in later life and highlights the importance of renal factors other than nephron number in the programming of renal and cardiovascular disease.
Highlights
Maternal stress is known to negatively impact fetal development and program long-term health deficits for the adult offspring (Harris and Seckl 2011; Moisiadis and Matthews 2014)
This study demonstrates for the first time in the mouse that maternal Cort exposure programs an increase in renal renin concentrations and Ren1 mRNA expression in male but not female offspring and this is associated with increased mRNA expression of additional key components of the renal RAS
This study demonstrates that maternal Cort exposure can dysregulate the renal renin–angiotensin–aldosterone system (RAAS) and induce minor impairments in renal physiology in male but not in female offspring
Summary
Maternal stress is known to negatively impact fetal development and program long-term health deficits for the adult offspring (Harris and Seckl 2011; Moisiadis and Matthews 2014). These programmed disease outcomes are often sex specific with cardiovascular and renal deficits being more prevalent or severe in males (Intapad et al 2014). Studies in animal models have shown that maternal exposure to glucocorticoids during pregnancy can impair kidney development, reduce nephron endowment, and program the development of disease in adulthood (Moritz et al 2005). There are many studies which have demonstrated an association between a nephron deficit and dysregulated blood pressure in adulthood, there is significant evidence to suggest that a nephron deficit alone is unlikely to cause disease and that a number of additional renal factors are likely to be involved (Dorey et al 2014)
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