The present study aimed to investigate the long‐term effects of exercise before pregnancy on changes induced by prenatal stress. Female and male Balb/c mice were divided into three groups: control (CON), prenatal restraint stress (PNS), and exercise before the gestational period plus PNS (EX + PNS). As adult, fear/anxiety behavior, corticosterone secretion, expression of hypothalamic‐pituitary‐adrenal (HPA)‐related genes, as well as epigenetic modifications were evaluated. Exercise before gestation did not prevent the increased fear/anxiety behavior in PNS mice. A nearly significant (p = .06) basal corticosterone increase was observed in PNS males and the exercise before pregnancy reduced the stress‐induced corticosterone increase in PNS females. In addition, an increase on prefrontal cortex (PFC) CRHR1 gene expression was observed in PNS females, which was attenuated by the exercise before gestation. We have also found a glucocorticoid receptor (GR) gene expression decrease in the prefrontal cortex in PNS males, as well as a histone H3 acetylation decrease (p = .06) close to the significance level. In conclusion, pregestational exercise may attenuate developmental changes induced by prenatal stress in a sex‐dependent manner.

Stressful events during the prenatal period have been related to hyperactive hypothalamic–pituitary–adrenal (HPA) axis responses as well as metabolic changes in adult life. Moreover, regular exercise may contribute to the improvement of the symptoms associated with stress and stress-related chronic diseases. Therefore, this study aims to investigate the effects of exercise, before the gestation period, on the metabolic changes induced by prenatal stress in adult mice. Female Balb/c mice were divided into three groups: control (CON), prenatal restraint stress (PNS) and exercise before the gestational period plus PNS (EX + PNS). When adults, the plasmatic biochemical analysis, oxidative stress, gene expression of metabolic-related receptors and sex differences were assessed in the offspring. Prenatal stress decreased neonatal and adult body weight when compared to the pregestational exercise group. Moreover, prenatal stress was associated with reduced body weight in adult males. PNS and EX + PNS females showed decreased hepatic catalase. Pregestational exercise prevented the stress-induced cholesterol increase in females but did not prevent the liver mRNA expression reduction on the peroxisome proliferator-activated receptors (PPARs) α and γ in PNS females. Conversely, PNS and EX + PNS males showed an increased PPARα mRNA expression. In conclusion, pregestational exercise prevented some effects of prenatal stress on metabolic markers in a sex-specific manner.

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