A new 'Crowded uterine horn' mouse model for examining the relationship between foetal growth and adult obesity
A new 'Crowded uterine horn' mouse model for examining the relationship between foetal growth and adult obesity
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DOI：
10.1111/j.1742-7843.2007.00195.x
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发表时间：
2008-02-01
影响因子：
3.1
通讯作者：
vom Saal, Frederick S.
中科院分区：
文献类型：
--
作者：
Coe, Benjamin L.;Kirkpatrick, James R.;vom Saal, Frederick S.
肥胖不仅在发达国家而且在全世界都是一个日益严重的健康问题。除了关注食物摄入和能量消耗之外，目前的研究还表明对成人体重的另外两个重要影响：出生体重和产后生长率。实验室动物研究中检查低出生体重与成年肥胖之间关系的常用程序是母亲营养限制，但母亲营养不良并不是发达国家大多数肥胖个体的基础。因此，我们开发了一种新的人类肥胖小鼠模型，称为“拥挤子宫角模型”。通过切除雌性 CD-1 小鼠的一个卵巢，雌性在一个子宫角中产下约 13 只幼仔，导致一窝胎儿之间胎盘血流拥挤且差异 4 倍。胎盘血流受限导致宫内生长受限（IUGR）；这些动物在断奶后一周内体重增加了两倍，而巨大胎儿在产后同一时期的生长量非常小。出生时被分类为 IUGR 或巨大体的雄性小鼠在成年后均肥胖。雄性小鼠一生中体重变化的模式反映了对 IUGR 和巨大儿肥胖的人类胎儿的流行病学研究结果，因此可能提供一个反映发达国家肥胖人群状况的新模型。
Obesity is an increasing health problem, not only in developed countries but also all over the world. In addition to the focus on food intake and energy expenditure, current studies suggest two other important influences on adult body weight: birth weight and postnatal rate of growth. A common procedure in laboratory animal studies to examine the relationship of low birth weight and adult obesity is maternal nutrient restriction, but maternal undernutrition is not the basis for the majority of obese individuals in developed countries. We have thus developed a new mouse model for human obesity referred to as 'the crowded uterine horn model'. By removing one ovary from a female CD-1 mouse, the female produces a litter of about 13 pups in one uterine horn, resulting in crowding and a 4-fold difference in placental blood flow among foetuses in a litter. Restricted placental blood flow results in intrauterine growth restriction (IUGR); these animals show a 2-fold increase in body weight during the week after weaning, while macrosomial foetuses that go through a very small amount of growth during the same postnatal period. Male mice categorized as IUGR or macrosomic at birth both are obese in adulthood. This pattern of changes in body weight throughout life in male mice mirrors findings from epidemiological studies of human foetuses with IUGR and macrosomia who become obese, and thus may provide a new model that reflects the condition of people in developed countries who become obese.