Abstract
Prenatal hypoxia is a gestational stressor that can result in developmental abnormalities or physiological reprogramming, and often decreases cellular capacity against secondary stress. When a developing fetus is exposed to hypoxia, blood flow is preferentially redirected to vital organs including the brain and heart over other organs including the kidney. Hypoxia-induced injury can lead to structural malformations in the kidney; however, even in the absence of structural lesions, hypoxia can physiologically reprogram the kidney leading to decreased function or increased susceptibility to injury. Our investigation in mice reveals that while prenatal hypoxia does not affect normal development of the kidneys, it primes the kidneys to have an increased susceptibility to kidney injury later in life. We found that our model does not develop structural abnormalities when prenatally exposed to modest 12% O2 as evident by normal histological characterization and gene expression analysis. Further, adult renal structure and function is comparable to mice exposed to ambient oxygen throughout nephrogenesis. However, after induction of kidney injury with a nephrotoxin (cisplatin), the offspring of mice housed in hypoxia exhibit significantly reduced renal function and proximal tubule damage following injury. We conclude that exposure to prenatal hypoxia in utero physiologically reprograms the kidneys leading to increased susceptibility to injury later in life.