Abstract:Aim To investigate whether maternal exercise can reduce the susceptibility of adult offspring from obese dams to cerebral ischemia-reperfusion injury. Methods Female C57BL/6J mice were fed either normal chow diet (NCD, 10% kCal from fat) or high-fat diet (HFD, 60% kCal from fat) starting at 5 weeks of age. After 8 weeks, the female mice were randomly assigned to four groups:normal chow diet and sedentary (NCD-SED), normal chow diet and exercise (NCD-EX), high-fat diet and sedentary (HFD-SED), and high-fat diet and exercise (HFD-EX). The female mice in the exercise groups underwent unloaded swimming (32～34 ℃, 20 cm deep, for 60 min/day, 6 days/week). After the 4-week exercise intervention, female mice were paired with males fed a normal diet for mating at a 2∶1 ratio. The day when a vaginal plug was detected and sperm were verified by vaginal cytology was defined as gestational day 1 (GD1). During gestation, exercise was continued for dams in the exercise groups (45 min/day, 5 days/week). Maternal pre-pregnancy body weight, body composition and glucose tolerance were assessed, and fetal growth parameters and placental efficiency were evaluated at term. Subsequently, 3-month-old offspring were selected as research subjects to establish the transient middle cerebral artery occlusion/reperfusion (tMCAO/R) model, and the cerebral infarct area was measured. Results (1) Pre-pregnancy body weight, body fat percentage, and the area under the curve for the glucose tolerance test were significantly higher in HFD-SED dams than those in NCD-SED dams (P＜0.01), whereas these metrics were significantly lower in HFD-EX dams than those in HFD-SED dams (P＜0.05). (2) Body weight during gestational was consistently higher in the HFD-SED group than that in the NCD-SED group (P＜0.05). From GD15 to GD18, the body weight of HFD-EX dams was significantly lower than that of HFD-SED dams (P＜0.05). There was no significant difference in litter size among the groups. (3) No significant difference was observed in the body length of fetuses among all groups (P＞0.05). The HFD-SED group exhibited significantly higher fetal weight and placental weight (P＜0.01), but significantly lower placental efficiency (P＜0.01) than those in the NCD-SED group. Conversely, fetal weight and placental weight were significantly decreased, while placental efficiency was significantly increased in the HFD-EX group compared with the HFD-SED group (P＜0.01). (4) At 3 months of age, the body weight and body fat of both male and female offspring were significantly higher in the HFD-SED group than in the NCD-SED group, whereas they were significantly decreased in the HFD-EX group compared with the HFD-SED group (P＜0.05). (5) Compared with the NCD-SED group, offspring of the HFD-SED group showed a significantly larger cerebral infarct area induced by tMCAO/R injury (P＜0.05). However, maternal exercise significantly reduced the infarct area in the offspring of the HFD-EX group (P＜0.05). Conclusion Maternal aerobic exercise mitigates high-fat diet-induced fetal overgrowth and excessive adiposity in adult offspring, and reduces their susceptibility to cerebral ischemia-reperfusion injury.
