How developmental stressors affect mitochondrial respiratory function: a systematic review and meta-analysis

The environmental conditions organisms experience during early development can have powerful and sustained effects on morphology, physiology, behaviour, and performance. Such developmental effects can influence reproductive success, survival, and life-history strategies and can be transmitted across generations (i.e. trans and intergenerational effects). In this way, developmental effects can be powerful drivers of evolutionary change. Given the developmental environment affects a range of phenotypic traits, it has been proposed that physiological responses to developmental conditions are modulated through cellular mechanisms that are shared across cell and tissue types, such as mitochondrial function. Mitochondrial respiratory function is highly sensitive to environmental conditions and exposure to adverse conditions during development can have sustained effects on different aspects of aerobic respiration in mitochondria. However, it is currently unknown if these effects are widespread across taxonomic groups and which components of mitochondrial respiratory function are most likely to be affected by the environment during development. We compiled data from 86 studies to examine the effects of developmental stressors (nutritional imbalance, glucocorticoid hormone exposure, parental care deprivation, and psychological disturbance) on mitochondrial respiratory function using meta-analysis. We sought to uncover whether there are general effects of developmental stressors on different aspects of mitochondrial respiratory function (antioxidants, metabolic capacity, oxidative damage, oxidative stress, and aerobic respiration). We tested how the type of developmental stressor, together with timing of exposure (prenatal versus postnatal), and sex and taxon of the test subjects influenced the magnitude, direction, and duration of effects on mitochondrial respiratory function. Finally, we tested which aspects of mitochondrial respiratory function were most impacted by developmental stressors. We found that exposure to glucocorticoids, parental care deprivation, and psychological disturbances during development generally decreased mitochondrial respiratory function. Generally, these developmental stressors increased the production of reactive oxygen species and oxidative damage and reduced aerobic respiration, metabolic capacity, and antioxidant levels. Nutritional imbalances during development (including both restricted and excessive nutrition) had a slight negative effect on mitochondrial respiratory function, but this effect may be influenced by publication bias. Overall, our results show that exposure to stressors during development negatively affects mitochondrial respiratory function, suggesting that changes in cellular metabolism may link developmental stressors to variation in whole animal traits and individual fitness.