Effects of antenatal melatonin therapy on lung structure in growth-restricted newborn lambs

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)1195-1203
Number of pages9
JournalJournal of Applied Physiology
Volume123
Issue number5
DOIs
Publication statusPublished - 1 Nov 2017

Keywords

  • Antioxidant
  • Fetal growth restriction
  • Intrauterine growth restriction
  • Melatonin
  • Small for gestational age

Cite this

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title = "Effects of antenatal melatonin therapy on lung structure in growth-restricted newborn lambs",
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.",
keywords = "Antioxidant, Fetal growth restriction, Intrauterine growth restriction, Melatonin, Small for gestational age",
author = "Polglase, {Graeme R.} and Jade Barbuto and Allison, {Beth J.} and Tamara Yawno and Sutherland, {Amy E.} and Atul Malhotra and Schulze, {Keith E.} and Wallace, {Euan M.} and Graham Jenkin and Ricardo, {Sharon D.} and Miller, {Suzanne L.}",
year = "2017",
month = "11",
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doi = "10.1152/japplphysiol.00783.2016",
language = "English",
volume = "123",
pages = "1195--1203",
journal = "Journal of Applied Physiology",
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publisher = "American Physiological Society",
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}

Effects of antenatal melatonin therapy on lung structure in growth-restricted newborn lambs. / Polglase, Graeme R.; Barbuto, Jade; Allison, Beth J.; Yawno, Tamara; Sutherland, Amy E.; Malhotra, Atul; Schulze, Keith E.; Wallace, Euan M.; Jenkin, Graham; Ricardo, Sharon D.; Miller, Suzanne L.

In: Journal of Applied Physiology, Vol. 123, No. 5, 01.11.2017, p. 1195-1203.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Effects of antenatal melatonin therapy on lung structure in growth-restricted newborn lambs

AU - Polglase, Graeme R.

AU - Barbuto, Jade

AU - Allison, Beth J.

AU - Yawno, Tamara

AU - Sutherland, Amy E.

AU - Malhotra, Atul

AU - Schulze, Keith E.

AU - Wallace, Euan M.

AU - Jenkin, Graham

AU - Ricardo, Sharon D.

AU - Miller, Suzanne L.

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N2 - 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.

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KW - Antioxidant

KW - Fetal growth restriction

KW - Intrauterine growth restriction

KW - Melatonin

KW - Small for gestational age

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U2 - 10.1152/japplphysiol.00783.2016

DO - 10.1152/japplphysiol.00783.2016

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