Early life parameters and personality affect oxidative status during adulthood in an altricial rodent

Abstract

It is increasingly recognized that alterations of the cellular oxidative status might be an important cost underlying challenging early life conditions. For example, an increased litter size can impose challenges as the offspring will face increased competition for maternal resources. Within a litter, individuals with relatively higher starting mass typically show higher growth rates, which can lead to increased oxidative damage. We investigated the long-term consequences of these early life parameters on the oxidative status in mature mound-building mice (Mus spicilegus). Individual differences in the animals' exploration tendency were assessed by repeated open field and novel object tests. We predicted less exploratory phenotypes, which typically show a higher stress responsiveness, to be particularly susceptible to possible effects of these early life parameters on oxidative status. We quantified oxidative damage of DNA (8-hydroxy-2'-deoxyguanosine levels, 8-OHdG) and proteins (protein carbonyl content, PCC), and activities of the antioxidants catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) in liver and skeletal muscle tissue. 8-OHdG levels were positively associated with CAT and SOD in both tissues, indicating that increased oxidative DNA damage was associated with an upregulation of antioxidant production. Hepatic DNA damage after maturity was increased in animals from larger litters. In less exploratory animals, DNA damage and the activity of CAT and SOD in the muscle were increased, but only in individuals with higher relative starting mass (measured on postnatal day 9). This interaction may be explained by the typically higher adrenocortical activity in less exploratory phenotypes and by the higher growth in relatively heavier pups, two factors known to increase oxidative stress. These findings contribute to enlightening the complex interplay between early life conditions, personality, and oxidative status.

Keywords: Mus spicilegus; DNA damage; exploration tendency; litter size; mound-building mouse; oxidative stress.

FIGURE 1

Association between the original litter size of female mound‐building mice (n = 35 females from 15 litters) and their 8‐hydroxy‐2′‐deoxyguanosine concentration (as a marker of oxidative DNA damage) in the liver at adult age (4.8 months). The three conditions plotted for each significant interaction are exemplary categorizations (low: 10% percentile, medium: 50% percentile, high: 90% percentile) of the females' within‐litter body mass ranking prior to weaning (continuous variable, see Table 2). The regression line with 95% confidence intervals (gray shading) is based on parameter estimates of a linear mixed‐effects model given in Table 2a.

FIGURE 2

Interactive effects of exploratory activity (PCA score, see text) and the ranked within‐litter pup body mass (0 = lightest, 1 = heaviest pup per litter) on different parameters of oxidative status measured in adult female mound‐building mice (n = 35 animals from 15 litters; 4.8 months old). The three conditions plotted for each significant interaction are exemplary categorizations (low: 10% percentile, medium: 50% percentile, high: 90% percentile) of the females' within‐litter body mass ranking prior to weaning (continuous variable, see Table 2). The regression lines with 95% confidence intervals (gray shading) are based on parameter estimates of linear mixed‐effects models given in Table 2.