Prenatal hypoxia increases susceptibility to kidney injury

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% O 2 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.

Evaluation of Fetal Renal Artery Doppler Indices in Pregnancies Complicated with Preeclampsia

“…Fetal peripheral circulation, including renal arteries, is sensitive to neurohumoral stimulation owing to acidosis and hypoxia. Arterial vasoconstriction occurs in the presence of acidosis and hypoxia, and the fetal renal artery blood flow decreases [21, 22]. The uteroplacental circulation is impaired in pregnancies with hypertensive disorders, and this impaired circulation is correlated with adverse perinatal outcomes [16, 23].…”

Allogeneic bone marrow mesenchymal stem cell-derived exosomes alleviate human hypoxic AKI-on-a-Chip within a tight treatment window

“…As a preventable cause of morbidity and mortality, extensive research is needed for prevention of AKI as underlined by International Society of Nephrology (ISN)’s 0by25 initiative [ 6 ]. Current experimental models for research involving cell monolayers [ 7 – 14 ] and in vivo animal settings [ 15 – 18 ] evaluate hypoxic PT injury for theragnostic approaches to some extent. The human monolayer renal parenchymal cell cultures even though easy to set [ 19 ], provide poor epithelial polarization that may cause low levels of key protein transporters [ 20 ], no output on PT ultrafiltrate flow [ 21 ] and do not contain any of the stromal microenvironmental elements [ 22 ].…”

Prenatal Hypoxia and Placental Oxidative Stress: Insights from Animal Models to Clinical Evidences

“…Therefore, fetal hypoxia, due to alterations of fetal programming, represents an immediate danger to fetal life, but also to the future life [9]. Indeed, the exposure of the fetus to hypoxic conditions predisposes the offspring to congenital anomalies and chronic diseases, such as cardiovascular, renal and metabolic disorders, in later life [3,[11][12][13][14][15][16].…”