Maternal creatine supplementation from mid-pregnancy protects the diaphragm of the newborn spiny mouse from intrapartum hypoxia-induced damage

We hypothesized that maternal creatine supplementation from mid-pregnancy would protect the newborn spiny mouse diaphragm from the effects of intrapartum hypoxia. Pregnant mice were fed a control or 5 creatine-supplemented diet from mid-gestation. On the day before term, intrapartum hypoxia was induced by isolating the pregnant uterus in a saline bath for 7.5-8 mins before releasing and resuscitating the fetuses. Surviving pups were placed with a cross-foster dam, and diaphragm tissue collected at 24 h postnatal age. Hypoxia caused a significant decrease in the cross-sectional area ( approximately 19 ) and contractile function (26.6 decrease in maximum Ca-activated force) of diaphragm fibres. mRNA levels of the muscle mass-regulating genes MuRF1 and myostatin were significantly increased (2-fold). Maternal creatine significantly attenuated hypoxia-induced fibre atrophy, contractile dysfunction and changes in mRNA levels. This study demonstrates that creatine-loading before birth significantly protects the diaphragm from hypoxia-induced damage at birth. ABBREVIATIONS::