The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
J Appl Physiol (1985). 2017 Nov 1;123(5):1195-1203. doi: 10.1152/japplphysiol.00783.2016. Epub 2017 Aug 17.
Oxidative stress arising from suboptimal placental function contributes to a multitude of pathologies in infants compromised by fetal growth restriction (FGR). FGR infants are at high risk for respiratory dysfunction after birth and poor long-term lung function. Our objective was to investigate the contribution of oxidative stress to adverse lung development and the effects of melatonin administration, a powerful antioxidant, on lung structure in FGR lambs. Placental insufficiency and FGR was surgically induced in 13 fetal sheep at ∼105 days of gestation by ligation of a single umbilical artery. Maternal intravenous melatonin infusion was commenced in seven of the ewes 4 h after surgery and continued until birth. Lambs delivered normally at term and lungs were collected 24 h after birth for histological assessment of lung structure and injury and compared with appropriately grown control lambs ( = 8). FGR fetuses were hypoxic and had lower glucose during gestation compared with controls. Melatonin administration prevented chronic hypoxia. Within the lung, FGR caused reduced secondary septal crest density and altered elastin deposition compared with controls. Melatonin administration had no effect on the changes to lung structure induced by FGR. We conclude that chronic FGR disrupts septation of the developing alveoli, which is not altered by melatonin administration. These findings suggest that oxidative stress is not the mechanism driving altered lung structure in FGR neonates. Melatonin administration did not prevent disrupted airway development but also had no apparent adverse effects on fetal lung development. Fetal growth restriction (FGR) results in poor respiratory outcomes, which may be caused by oxidation in utero. We investigated the contribution of oxidative stress to adverse lung development and the effects of melatonin administration, a powerful antioxidant, on lung structure in FGR lambs. FGR disrupted septation of the developing alveoli, which is not altered by melatonin administration. Oxidative stress may not be the mechanism driving altered lung structure in FGR neonates.
胎盘功能不佳导致的氧化应激会引发多种病理变化，使胎儿生长受限（FGR）的婴儿受到影响。FGR 婴儿在出生后存在呼吸功能障碍和长期肺功能不良的高风险。我们的目的是研究氧化应激对不良肺发育的贡献，以及褪黑素（一种强大的抗氧化剂）对 FGR 羔羊肺部结构的影响。通过结扎单根脐带动脉，在大约 105 天的胎羊中进行了胎盘功能不全和 FGR 的手术诱导。在手术后 4 小时，7 只母羊开始接受静脉褪黑素输注，并持续到分娩。羔羊正常足月分娩，出生后 24 小时收集肺部进行组织学评估，以评估肺结构和损伤，并与适当生长的对照组羔羊（=8）进行比较。FGR 胎儿在妊娠期间缺氧，血糖水平低于对照组。褪黑素的给予可预防慢性缺氧。在肺部，FGR 导致次级隔嵴密度降低，并改变了弹性蛋白的沉积，与对照组相比有差异。褪黑素的给予对 FGR 引起的肺结构变化没有影响。我们的结论是，慢性 FGR 破坏了发育中的肺泡的分隔，而褪黑素的给予并不能改变这一点。这些发现表明，氧化应激不是导致 FGR 新生儿肺部结构改变的机制。褪黑素的给予并未阻止气道发育的中断，但对胎儿肺部发育也没有明显的不良影响。胎儿生长受限（FGR）会导致呼吸功能不良，这可能是由于宫内氧化作用引起的。我们研究了氧化应激对不良肺发育的贡献，以及褪黑素（一种强大的抗氧化剂）对 FGR 羔羊肺部结构的影响。FGR 破坏了发育中的肺泡的分隔，而褪黑素的给予并不能改变这一点。氧化应激可能不是导致 FGR 新生儿肺部结构改变的机制。
