Transient neonatal exposure to hyperoxia, an experimental model of preterm birth, leads to skeletal muscle atrophy and fiber type switching

Abstract

Individuals born preterm show reduced exercise capacity and increased risk for pulmonary and cardiovascular diseases, but the impact of preterm birth on skeletal muscle, an inherently critical part of cardiorespiratory fitness, remains unknown. We evaluated the impacts of preterm birth-related conditions on the development, growth, and function of skeletal muscle using a recognized preclinical rodent model in which newborn rats are exposed to 80% oxygen from day 3 to 10 of life. We analyzed different hindlimb muscles of male and female rats at 10 days (neonatal), 4 weeks (juvenile) and 16 weeks (young adults). Neonatal high oxygen exposure increased the generation of reactive oxygen species and the signs of inflammation in skeletal muscles, which was associated with muscle fiber atrophy, fiber type shifting (reduced proportion of type I slow fibers and increased proportion of type IIb fast-fatigable fibers), and impairment in muscle function. These effects were maintained until adulthood. Fast-twitch muscles were more vulnerable to the effects of hyperoxia than slow-twitch muscles. Male rats, which expressed lower antioxidant defenses, were more susceptible than females to oxygen-induced myopathy. Overall, preterm birth-related conditions have long-lasting effects on the composition, morphology, and function of skeletal muscles; and these effects are sex-specific. Oxygen-induced changes in skeletal muscles could contribute to the reduced exercise capacity and to increased risk of diseases of preterm born individuals.

Neonatal hyperoxia leads to white adipose tissue remodeling and susceptibility to hypercaloric diet

“…Our findings show that neonatal hyperoxia exposure leads to pWAT remodeling with significant fibrosis, which is in accordance with enhanced fibrosis reported in the lungs, heart, and skeletal muscles in this experimental model (Bertagnolli, Dios, et al, 2016 ; Chen et al, 2007 ; Deprez et al, 2021 ). Taken together, these studies suggest that tissue fibrosis may be a common manifestation of tissue injury following transient neonatal hyperoxia.…”

“…Indeed, under pathological conditions, adipose tissue remodeling is characterized and accelerated by immune cell infiltration (DeBari & Abbott, 2020 ; Hotamisligil et al, 1993 ). Expansion of macrophage density was also previously observed in the same model in adulthood and in males cardiac left ventricle (Mian et al, 2019 ), skeletal muscle (Deprez et al, 2021 ). Low‐grade chronic inflammation can induce macrophage infiltration mediated by the release of MCP1 from resident adipocytes (Kanda et al, 2006 ; Sartipy & Loskutoff, 2003 ; Weisberg et al, 2006 ).…”

“…We previously showed in a well‐established and clinically relevant rodent model mimicking preterm birth associated conditions that transient neonatal exposure to hyperoxia‐induced long‐term cardiovascular, renal, and muscular alterations (Deprez et al, 2021 ; O'Reilly & Thébaud, 2014 ; Ravizzoni Dartora et al, 2022 ; Yzydorczyk et al, 2008 ) associated with oxidative stress and inflammation (Bertagnolli et al, 2014 ; Mian et al, 2019 ). Indeed, transient neonatal rat exposure to high concentrations of oxygen mimics the combination of a sudden and sustained rise in partial pressure of oxygen (pO 2 ) associated with birth in an immature organism (O'Reilly & Thébaud, 2014 ).…”

HAPI Fit: An Exercise Intervention to Improve Peak Aerobic Capacity in Young Adults Born Very Preterm

“…Mechanisms for reduced exercise capacity after preterm birth remain to be elucidated (33). Some hypotheses have been discussed before and include smaller airways, which can lead to airflow limitation, impaired cardiac response to exercise through smaller cardiac chamber, and impaired myocardial functional reserve, along with a certain degree of pulmonary hypertension in some individuals, and reduced skeletal muscle strength and development (40,41). Studies to identify pathways that are the most amenable to change after preterm birth could allow the design of more targeted exercise interventions.…”

Clearance of defective muscle stem cells by senolytics restores myogenesis in myotonic dystrophy type 1

“…The supernatant was retained, aliquoted, and the protein content was quantified using the BCA Assay Kit (Thermo scientific, Mississauga, Ontario, Canada). A volume corresponding to 40 μg of protein was diluted with a sample buffer (125 mM Tris buffer (pH 6.8), 4% SDS, 20% glycerol, 0.05% bromophenol blue, and 200 mM dithiothreitol), heated at 100 °C for 5 min and electroseparated on 10% sodium dodecyl sulfate-polyacrylamide gel 103 . Proteins were transferred to polyvinylidene difluoride membranes, which were blocked with 5% non-fat milk or 5% BSA for 90 min at room temperature.…”