Using a rabbit model, we investigated whether maternal intake of a high-fat and high-carbohydrate diet (HFCD) before and during pregnancy induces an increase in micronuclei frequency and oxidative stress in offspring during adulthood. Female rabbits received a standard diet (SD) or HFCD for two months before mating and during gestation. The offspring from both groups were nursed by foster mothers fed SD until postnatal day 35. After weaning, all the animals received SD until postnatal day 440. At postnatal day 370, the frequency of micronuclei in peripheral blood reticulocytes (MN-RETs) increased in the male offspring from HFCD-fed mothers compared with the male offspring from SD-fed mothers. Additionally, fasting serum glucose increased in the offspring from HFCD-fed mothers compared with the offspring from SD-fed mothers. At postnatal day 440, the offspring rabbits were challenged with HFCD or continued with SD for 30 days. There was an increase in MN-RET frequency in the male rabbits from HFCD-fed mothers, independent of the type of challenging diet consumed during adulthood. The challenge induced changes in serum cholesterol, LDL and HDL that were influenced by the maternal diet and offspring sex. We measured malondialdehyde in the liver of rabbits as an oxidative stress marker after diet challenge. Oxidative stress in the liver only increased in the female offspring from HFCD-fed mothers who were also challenged with this same diet. The data indicate that maternal overnutrition before and during pregnancy is able to promote different effects depending on the sex of the animals, with chromosomal instability in male offspring and oxidative stress and hypercholesterolemia in female offspring. Our data might be important in the understanding of chronic diseases that develop in adulthood due to in utero exposure to maternal diet.

使用兔子模型，我们调查了母体在怀孕前和怀孕期间摄入高脂肪和高碳水化合物饮食 (HFCD) 是否会导致后代成年期微核频率和氧化应激的增加。雌兔在交配前和妊娠期间接受标准饮食 (SD) 或 HFCD 两个月。两组的后代均由养母喂养至出生后第 35 天。断奶后，所有动物均接受 SD 至出生后第 440 天。在出生后第 370 天，外周血网织红细胞 (MN-RET) 中的微核频率增加HFCD 喂养的母亲的雄性后代与 SD 喂养的母亲的雄性后代相比。此外，与喂食 SD 的母亲的后代相比，喂食 HFCD 的母亲的后代的空腹血糖升高。在产后第 440 天，后代兔接受 HFCD 攻击或继续接受 SD 治疗 30 天。来自 HFCD 喂养的母亲的雄性兔子的 MN-RET 频率增加，与成年期间消耗的挑战性饮食类型无关。挑战引起血清胆固醇、低密度脂蛋白和高密度脂蛋白的变化，这些变化受母体饮食和后代性别的影响。我们测量了兔子肝脏中的丙二醛作为饮食挑战后的氧化应激标志物。肝脏中的氧化应激仅在来自 HFCD 喂养的母亲的雌性后代中增加，这些母亲也接受了同样的饮食挑战。数据表明，孕前和孕期母体营养过剩能够根据动物的性别产生不同的影响，与雄性后代的染色体不稳定性和雌性后代的氧化应激和高胆固醇血症有关。我们的数据可能对理解由于以下原因导致的成年期慢性疾病很重要子宫内暴露于母体饮食。