Diet-Induced Obesity Model: Abnormal Oocytes and Persistent Growth Abnormalities in the Offspring
Diet-Induced Obesity Model: Abnormal Oocytes and Persistent Growth Abnormalities in the Offspring
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DOI：
10.1210/en.2010-0098
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发表时间：
2010-08-01
期刊：
影响因子：
4.8
通讯作者：
Moley, Kelle H.
中科院分区：
文献类型：
--
作者：
Jungheim, Emily S.;Schoeller, Erica L.;Moley, Kelle H.
母体肥胖和不良胎儿结局之间的关系已有大量文献记载，但其机制尚不清楚。之前的大多数工作都集中在孕后事件上，然而，我们的实验室已经表明，母体葡萄糖代谢的孕前和孕周异常会对卵母细胞和胚胎产生不利影响，并会遗传给胎儿。为了证明母体肥胖在受孕前和受孕期的影响，我们比较了饮食诱导肥胖雌性小鼠和对照小鼠的生殖组织。对卵巢进行卵泡凋亡染色或解剖并评价卵母细胞大小和减数分裂成熟。还对小鼠进行交配并随访生殖结果，包括植入前胚胎IGF-I受体（IGF-IR）免疫染色、妊娠中期胎儿生长和妊娠中期胎盘IGF受体2（Igf 2 r）mRNA。跟踪分娩的幼仔的生长和代谢综合征标志物的发展。与对照组相比，肥胖小鼠有更多的凋亡卵泡，更小和更少的成熟卵母细胞，减少胚胎IGF-IR染色，更小的胎儿，胎盘Igf 2 r mRNA增加，和更小的幼崽。所有断奶的幼仔均喂食常规饮食。13周时，肥胖小鼠的幼崽明显较大，这些幼崽表现出葡萄糖耐受不良和胆固醇和体脂增加，表明代谢型综合征的早期发展。总之，我们的研究结果表明，母体肥胖早在卵母细胞和植入前胚胎阶段就有不良影响，这些影响可能导致后代的持续发病率，强调了怀孕前最佳母体体重和营养的重要性。（内分泌学151：4039-4046，2010）
Associations between maternal obesity and adverse fetal outcomes are well documented, but the mechanisms involved are largely unknown. Most previous work has focused on postconceptional events, however, our laboratory has shown pre-and periconceptional aberrations in maternal glucose metabolism have adverse effects on oocytes and embryos that carry on to the fetus. To demonstrate effects of maternal obesity in the pre-and periconceptional periods, we compared reproductive tissues from diet-induced obese female mice to those of control mice. Ovaries were either stained for follicular apoptosis or dissected and evaluated for oocyte size and meiotic maturation. Mice were also mated and followed for reproductive outcomes including preimplantation embryonic IGF-I receptor (IGF-IR) immunostaining, midgestation fetal growth, and midgestational placental IGF receptor 2 (Igf2r) mRNA. Delivered pups were followed for growth and development of markers of metabolic syndrome. Compared with controls, obese mice had significantly more apoptotic ovarian follicles, smaller and fewer mature oocytes, decreased embryonic IGF-IR staining, smaller fetuses, increased placental Igf2r mRNA, and smaller pups. All weaned pups were fed a regular diet. At 13 wk pups delivered from obese mice were significantly larger, and these pups demonstrated glucose intolerance and increased cholesterol and body fat suggesting early development of a metabolic-type syndrome. Together, our findings suggest maternal obesity has adverse effects as early as the oocyte and preimplantation embryo stage and that these effects may contribute to lasting morbidity in offspring, underscoring the importance of optimal maternal weight and nutrition before conception. (Endocrinology 151: 4039-4046, 2010)