title: Effect of maternal steroid on developing diaphragm integrity.
abstract: Antenatal steroids reduce the severity of initial respiratory distress of premature newborn babies but may have an adverse impact on other body organs. The study aimed to examine the effect of maternal steroids on postnatal respiratory muscle function during development and elucidate the mechanisms underlying the potential myopathy in newborn rats. Pregnant rats were treated with intramuscular injections of 0.5 mg/kg betamethasone 7 d and 3 d before birth. Newborn diaphragms were dissected for assessment of contractile function at 2 d, 7 d or 21 d postnatal age (PNA), compared with age-matched controls. The expression of myosin heavy chain (MHC) isoforms and atrophy-related genes and activity of intracellular molecular signalling were measured using quantitative PCR and/or Western blot. With advancing PNA, neonatal MHC gene expression decreased progressively while MHC IIb and IIx isoforms increased. Protein metabolic signalling showed high baseline activity at 2 d PNA, and significantly declined at 7 d and 21 d. Antenatal administration of betamethasone significantly decreased diaphragm force production, fatigue resistance, total fast fibre content and anabolic signalling activity (Akt and 4E-BP1) in 21 d diaphragm. These responses were not observed in 2 d or 7 d postnatal diaphragm. Results demonstrate that maternal betamethasone treatment causes postnatal diaphragmatic dysfunction at 21 d PNA, which is attributed to MHC II protein loss and impairment of the anabolic signalling pathway. Developmental modifications in MHC fibre composition and protein signalling account for the age-specific diaphragm dysfunction.
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth, Western Australia, Australia; Centre for Neonatal Research and Education, School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Yong
authors.initials: Y
authors.lastname: Song
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Denise L
authors.initials: DL
authors.lastname: Demmer
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Pinniger
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth, Western Australia, Australia; Centre for Neonatal Research and Education, School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Tina
authors.initials: T
authors.lastname: Lavin
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Mia V
authors.initials: MV
authors.lastname: MacMillan
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth, Western Australia, Australia; Centre for Neonatal Research and Education, School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia; Women and Newborns Health Service, c/-King Edward Memorial and Princess Margaret Hospitals, Perth, Western Australia, Australia.
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Pillow
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bakker
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D003964:Diaphragm / Q000378:metabolism* / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D033261:Maternal-Fetal Relations / Q000502:physiology*; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D024501:Nonmuscle Myosin Type IIB / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012132:Respiratory Muscles / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013256:Steroids / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D013256:Steroids; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains