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Published on: July 30, 2016
Effects of antenatal melatonin therapy on lung structure in growth-restricted newborn lambs
Graeme R Polglase1,2, Jade Barbuto1, Beth J Allison1
1The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Insights
Fetal growth restriction (FGR) impairs lung development by disrupting alveolar septation. Antioxidant melatonin did not alter these structural changes, suggesting oxidative stress isn't the primary cause in FGR lambs.
Area of Science:
- Perinatal Medicine
- Developmental Biology
- Respiratory Physiology
Background:
- Suboptimal placental function in fetal growth restriction (FGR) leads to infant pathologies, including respiratory dysfunction.
- Oxidative stress is implicated in FGR-related adverse lung development and poor long-term lung function.
Purpose of the Study:
- To investigate the contribution of oxidative stress to altered lung development in FGR.
- To evaluate the effects of melatonin, an antioxidant, on lung structure in FGR lambs.
Main Methods:
- Surgically induced FGR in 13 fetal sheep via umbilical artery ligation.
- Administered maternal intravenous melatonin to seven ewes from surgery until birth.
- Assessed lung structure and injury histologically 24 hours after birth in term lambs.
Main Results:
- FGR lambs exhibited reduced secondary septal crest density and altered elastin deposition.
- Melatonin administration prevented chronic hypoxia in FGR fetuses.
- Melatonin did not alter the FGR-induced structural changes in the developing lung.
Conclusions:
- Chronic FGR disrupts alveolar septation development.
- Oxidative stress is unlikely to be the primary mechanism driving altered lung structure in FGR.
- Melatonin did not affect FGR-induced airway development but had no adverse effects.
Abstract:
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 (n = 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.NEW & NOTEWORTHY 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.
