Neonatal hyperoxia: effects on nephrogenesis and long-term glomerular structure

Abstract

Preterm neonates are born while nephrogenesis is ongoing and are commonly exposed to factors in the extrauterine environment that may impair renal development. Supplemental oxygen therapy exposes the preterm infant to a hyperoxic environment that may induce oxidative stress. Our aim was to determine the immediate and long-term effects of exposure to hyperoxia, during the period of postnatal nephrogenesis, on renal development. Newborn mice (C57BL/6J) were kept in a normoxic (room air, 21% oxygen) or a controlled hyperoxic (65% oxygen) environment from birth to postnatal day 7 ( P7d). From P7d, animals were maintained in room air until early adulthood at postnatal day 56 ( P56d) or middle age (10 mo; P10mo). Pups were assessed for glomerular maturity and renal corpuscle cross-sectional area at P7d (control n = 14; hyperoxic n = 14). Nephron number and renal corpuscle size were determined stereologically at P56d (control n = 14; hyperoxic n = 14) and P10mo (control n = 10; hyperoxic n = 10). At P7d, there was no effect of hyperoxia on glomerular size or maturity. In early adulthood ( P56d), body weights, relative kidney weights and volumes, and nephron number were not different between groups, but the renal corpuscles were significantly enlarged. This was no longer evident at P10mo, with relative kidney weights and volumes, nephron number, and renal corpuscle size not different between groups. Furthermore, hyperoxia exposure did not significantly accelerate glomerulosclerosis in middle age. Hence, our findings show no overt long-term deleterious effects of early life hyperoxia on glomerular structure.

Hyperoxia Exposure Impairs Nephrogenesis in the Neonatal Rat: Role of HIF-1α

“…In this regard, we have previously shown that 80% O 2 exposure in the neonatal period results in vascular rarefaction, hypertension, and reduced nephron number in the adult rat [13], similar to clinical outcomes seen in children and adults that were born preterm [3]–[5]. In contrast, a recent study in a mouse model (mice exposed to 65% O 2 from birth to postnatal day 7) showed no changes in nephron number [33]; the differences in findings between studies may relate to differences in the concentration of oxygen used, the postnatal days of exposure, and also susceptibilities of the animal model.…”

Effects of preterm birth and ventilation on glomerular capillary growth in the neonatal lamb kidney

“…Studies conducted previously in a rat model of neonatal hyperoxia exposure (80% O 2 P3-P10, a time of ongoing postnatal nephrogenesis), found reduced glomerular size in neonates and a 25% reduction in nephron number in adulthood, suggesting that the kidney is adversely affected [14, 39]. Conversely, neonatal hyperoxia exposure (65% O 2 ) did not have any adverse renal effects in a mouse model [40]. Unlike these rodent models, in this more clinically relevant large animal model, nephrogenesis in the lamb was already completed, mechanical ventilation was used (and for a shorter time period of 3 days), and all animals were initially exposed to 100% O 2 then weaned to lower concentrations.…”

Preterm Birth and/or Factors that Lead to Preterm Delivery: Effects on the Neonatal Kidney

“…Consequently, this can lead to a number of common morbidities of prematurity such as, retinopathy of prematurity, necrotizing enterocolitis and bronchopulmonary dysplasia [169]. In the kidney of the human neonate, oxidative stress has been reported to cause tubular injury [170] and it has been linked to impairment of nephrogenesis in animal studies [171]. In the rat model (where nephrogenesis is ongoing in the first two weeks after birth), a significant reduction of nephrons (25%) was reported in adulthood (25-35 weeks of age) [171] following exposure to 80% oxygen during the early postnatal period.…”