Hyperlipidic hypercholesterolemic diet in prepubertal rabbits affects gene expression in the embryo, restricts fetal growth and increases offspring susceptibility to obesity
Hyperlipidic hypercholesterolemic diet in prepubertal rabbits affects gene expression in the embryo, restricts fetal growth and increases offspring susceptibility to obesity
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DOI：
10.1016/j.theriogenology.2010.08.015
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发表时间：
2011-01-15
期刊：
影响因子：
2.8
通讯作者：
Chavatte-Palmer, P.
中科院分区：
文献类型：
--
作者：
Picone, O.;Laigre, P.;Chavatte-Palmer, P.
母体高胆固醇血症已被证明可导致兔胎儿宫内生长迟缓（IUGR）。从10周龄开始，给母兔喂食高胆固醇（0.2%）、高胆固醇（8%）（HH）或对照（C）饲料。在18周时对16只母兔（N = 8只HH和N = 8只C）实施安乐死，以评估交配前饲料对母兔的影响。从16-20细胞期（胚胎基因组活化期）的输卵管收集来自18只雌性（N = 9只HH和N = 9只C）的胚胎用于基因表达分析（微阵列和定量RT-PCR）。30只雌性动物（N = 16 HH和N = 14 C）自然交配，并通过超声监测胎仔生长。其中6只（N = 4只HH和N = 2只C）在妊娠D28处以安乐死，以收集胎仔和胎盘。最后，将剩余的24只足月分娩的母兔和窝仔交叉饲养并在数量上平衡，以根据生物母鼠和饲养母鼠（C-C、C-HH、HH-C、HH-HH）创建4组。监测生长直至断奶。从4组中选出的26只后代，在25周龄前喂食对照饲料，然后喂食EH饲料三周，所有雌鼠的生长速度和体重相似。转录组学分析证明了在胚胎基因组激活阶段HH胚胎中Adipophilin的过表达。通过定量RT-PCR证实了这一点。妊娠期超声从D9开始观察到IUGR，HH组28天胎儿体重、新生儿体重及脂肪沉积均显著降低（P < 0.05）。断奶后，HH-HH和HH-C仔代体重差异不显著，但两组仔代体重均显著高于C-C和C-HH仔代（P < 0.0001）。在饲喂HE饲料的3周期间，各组之间的摄食量差异不再显著，但体重差异仍然存在。在死后，HH母鼠的后代的腹部和肩胛间脂肪显著多于C母鼠的后代（P < 0.05），这些数据说明了母鼠在妊娠前和妊娠期间的营养对于建立和控制孕体的生长轨迹以及成年期疾病的发生的重要性。(C)2011 Elsevier Inc. All rights reserved.
Maternal hypercholesterolemia has been shown to lead to fetal intra-uterine growth retardation (IUGR) in rabbits. The effects of a long term maternal hyperlipidemic and hypercholesterolemic diet on embryo, fetal and post-natal development, have not been addressed so far.Rabbit does were fed either a hypercholesterolemic (0.2%) hyperlipidic (8%) (HH) or a control (C) diet from 10 weeks of age. Sixteen does (N = 8 HH and N = 8 C) were euthanized at 18 weeks to assess the effect of the diet on dams before mating. Embryos from 18 females (N = 9 HH and N = 9 C) were collected from the oviducts at the 16-20 cell stage (embryonic genome activation stage) for gene expression analysis (micro array and quantitative RT-PCR). Thirty females (N = 16 HH and N = 14 C) were mated naturally and fetal growth was monitored by ultrasound. Six of them (N = 4 HH and N = 2 C) were euthanized at D28 of gestation to collect fetuses and placentas. Finally, the remaining 24 does delivered at term and litters were cross fostered and equilibrated in number to create 4 groups according to the biological dam and the foster dam (C-C, C-HH, HH-C, HH-HH). Growth was monitored until weaning. A subset of 26 offspring from the 4 groups was fed the control diet until 25 weeks of age and then fed the EH diet for three weeks.All does had similar growth rates and bodyweight. Transcriptomic analyses evidenced an overexpression of Adipophilin in HH embryos at the stage of embryonic genome activation. This was confirmed by quantitative RT-PCR. During pregnancy, IUGR was observed from D9 by ultrasound and subsequently, fetal weight at 28 days, birthweight and fat deposition in newborn offspring were significantly decreased in HH (P < 0.05). After weaning, there was no significant difference for weight between HH-HH and HH-C offspring and both groups became significantly heavier (P < 0.0001) than C-C and C-HH offspring. During the 3 weeks when offspring were fed the HE diet, the differences in feed intake were no longer significant between groups but the differences in body weight remained. At post-mortem, offspring from HH does had significantly more abdominal and inter-scapular fat than offspring from C does (P < 0.05).These data illustrate the importance of maternal nutrition before and during gestation in the establishment and control of the growth trajectory of the conceptus and in the onset of disease in adult life. (C) 2011 Elsevier Inc. All rights reserved.