Role of hypoxia during nephrogenesis

Abstract

Mammals develop in a physiologically hypoxic state and the oxygen tension of different tissues in the embryo is precisely controlled. Deviation from normal oxygenation, such as what occurs in placental insufficiency, can disrupt development. Several studies demonstrate that intrauterine hypoxia has a negative effect on kidney development. As nascent nephrons are forming from nephron progenitors in the nephrogenic zone, they are exposed to varying oxygen tension by virtue of the development of the renal vasculature. Thus, nephrogenesis may be linked to oxygen tension. However, the mechanism(s) by which this occurs remains unclear. This review will focus on what is known about the molecular mechanisms that are active in physiological and pathological hypoxia, and their effects on kidney development.

Hypoxia: From Placental Development to Fetal Programming

“…Besides impairments in growth, hypoxia can mediate different complications in fetal health, for example, meconium aspiration, hematologic disturbances, cognitive dysfunction, cerebral palsy, compromised kidney development, and morphofunctional changes in the heart (Giussani et al, ; Hemker et al, ).…”

“…In brain development, hypoxia impairs neuron migration, differential neurogenesis, and alters neurotransmitters expression. Reduced number of nephrons is observed in individuals that were gestated in a hypoxic environment and, in this case HIF activation of vascular endothelial growth factor A signals to inhibit nephrogenesis and enhance tubulogenesis (Gunn and Bennet, ; Hutter et al, ; Hemker et al, ).…”

Mapping vascular and glomerular pathology in a rabbit model of neonatal acute kidney injury using MRI

“…The highly vascularized kidney is particularly vulnerable to the effects of preterm birth with 60% of glomerular development occurring in the third trimester (Hinchliffe, Sargent, Howard, Chan, & van Velzen, 1991). During this period of active nephrogenesis, fluctuations in tissue oxygenation (Hemker, Sims-Lucas, & Ho, 2016), renal perfusion, and exposures to medications (Kent et al, 2014;Kent, Brown, Broom, Broomfield, & Dahlstrom, 2012) can lead to a reduced glomerular number. In children, radiologic evaluations of the vasculature are limited due radiation exposure and sedation effects.…”

Prenatal hypoxia increases susceptibility to kidney injury

“…When prenatal hypoxia occurs, the developing fetus exhibits a preferential redirection of blood flow, including oxygen and nutrient supply, to the brain and heart over less vital organs such as the kidney [5,6]. Previous studies in mouse and rat models of prenatal hypoxia often utilize a chambered hypoxia device, where pregnant dams are housed at 12% O 2 [7,8]. These studies show that exposure to modest hypoxia in utero can impair pre-and post-natal development [9] and can induce epigenetic modifications [10].…”

“…During this time, a population of self-renewing cells called nephron progenitors rapidly proliferate then undergo differentiation to give rise to the glomerular and renal tubular epithelia of the mature nephron [15]. This process of nephron development occurs under physiological hypoxia (~1-9% O 2 ) [7], and although temporal changes in oxygen tension are normal, chronic hypoxia can be detrimental [16].…”