title: Maternal Creatine Supplementation during Pregnancy Prevents Long-Term Changes in Diaphragm Muscle Structure and Function after Birth Asphyxia.
abstract: Using a model of birth asphyxia, we previously reported significant structural and functional deficits in the diaphragm muscle in spiny mice, deficits that are prevented by supplementing the maternal diet with 5% creatine from mid-pregnancy. The long-term effects of this exposure are unknown. Pregnant spiny mice were fed control or 5% creatine-supplemented diet for the second half of pregnancy, and fetuses were delivered by caesarean section with or without 7.5 min of in-utero asphyxia. Surviving pups were raised by a cross-foster dam until 33±2 days of age when they were euthanized to obtain the diaphragm muscle for ex-vivo study of twitch tension and muscle fatigue, and for structural and enzymatic analyses. Functional analysis of the diaphragm revealed no differences in single twitch contractile parameters between any groups. However, muscle fatigue, induced by stimulation of diaphragm strips with a train of pulses (330 ms train/sec, 40 Hz) for 300 sec, was significantly greater for asphyxia pups compared with controls (p<0.05), and this did not occur in diaphragms of creatine + asphyxia pups. Birth asphyxia resulted in a significant increase in the proportion of glycolytic, fast-twitch fibres and a reduction in oxidative capacity of Type I and IIb fibres in male offspring, as well as reduced cross-sectional area of all muscle fibre types (Type I, IIa, IIb/d) in both males and females at 33 days of age. None of these changes were observed in creatine + asphyxia animals. Thus, the changes in diaphragm fatigue and structure induced by birth asphyxia persist long-term but are prevented by maternal creatine supplementation.
authors.affiliation: Ritchie Centre, Hudson Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
authors.forename: Domenic A
authors.initials: DA
authors.lastname: LaRosa
authors.affiliation: Ritchie Centre, Hudson Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
authors.forename: Stacey J
authors.initials: SJ
authors.lastname: Ellery
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria, Australia.
authors.forename: Helena C
authors.initials: HC
authors.lastname: Parkington
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia.
authors.forename: Rod J
authors.initials: RJ
authors.lastname: Snow
authors.affiliation: Ritchie Centre, Hudson Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Walker
authors.affiliation: Ritchie Centre, Hudson Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
authors.forename: Hayley
authors.initials: H
authors.lastname: Dickinson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D003401:Creatine / Q000627:therapeutic use*; D003964:Diaphragm / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D019587:Dietary Supplements / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D018763:Muscle Fatigue / Q000187:drug effects; D011247:Pregnancy
chemical_list: D003401:Creatine