Lanham S A, Roberts C, Cooper C, Oreffo R O C
Bone and Joint Research Group, Developmental Origins of Health and Disease, University of Southampton, Southampton, SO16 6YD, UK.
Osteoporos Int. 2008 Feb;19(2):147-56. doi: 10.1007/s00198-007-0443-8. Epub 2007 Aug 15.
Osteoporosis is believed to partly be programmed in utero. Rat dams were given a low protein diet during pregnancy and 135 offspring studied at different ages. Bone biochemistry showed altered characteristics. Altered in utero diet has consequences for later life.
Epidemiological studies suggest skeletal growth is programmed during intrauterine and early postnatal life. We have investigated this in a rat model of maternal protein insufficiency.
Dams received either 18% w/w (control) or 9% w/w (low protein) diet during pregnancy, and the offspring were studied at selected time points (4, 8, 12, 16, 20, 47 weeks).
Alkaline phosphatase activity in controls reached peak levels from 8 to 20 weeks of age. In contrast, restricted diet offspring were at peak levels from 4 weeks of age. Peak levels were similar in both groups. Serum IGF-1 levels were lower in female restricted diet offspring at 4 weeks of age, and serum osteocalcin was significantly higher at 4 weeks of age in male and female offspring from mothers fed the restricted diet, whereas serum 25-OH vitamin D was significantly lower in restricted diet males at 8, 12, and 20 weeks of age.
These data indicate that a low protein diet in utero affected the osteogenic environment in the offspring with effects that persist into late adulthood. These results indicate the key role of the nutritional environment in early development on programming of skeletal development with implicit consequences in later life.
骨质疏松症被认为部分是在子宫内就已被编程的。妊娠期间给大鼠母鼠喂食低蛋白饮食，并对135只后代在不同年龄进行研究。骨生物化学显示出特征改变。子宫内饮食的改变对后期生活有影响。
流行病学研究表明，骨骼生长是在子宫内和出生后早期阶段被编程的。我们在母体蛋白质不足的大鼠模型中对此进行了研究。
妊娠期间母鼠接受18% w/w（对照）或9% w/w（低蛋白）饮食，并在选定时间点（4、8、12、16、20、47周）对后代进行研究。
对照组碱性磷酸酶活性在8至20周龄达到峰值水平。相比之下，饮食受限的后代在4周龄时就达到了峰值水平。两组的峰值水平相似。4周龄时，饮食受限的雌性后代血清IGF-1水平较低，而喂食受限饮食的母鼠所生的雄性和雌性后代在4周龄时血清骨钙素显著较高，而饮食受限的雄性大鼠在8、12和20周龄时血清25-OH维生素D显著较低。
这些数据表明，子宫内低蛋白饮食会影响后代的成骨环境，其影响会持续到成年后期。这些结果表明早期发育中的营养环境在骨骼发育编程中起关键作用，并对后期生活有潜在影响。
