Gruslin Andrée, Cesta Carolyn E, Bell Michael, Petre Maria A, Holloway Alison C
Division Maternal-Fetal Medicine, Department OBS-GYN and Newborn Care, The Ottawa Hospital University of Ottawa, Ontario, Canada.
Reprod Sci. 2009 Sep;16(9):875-82. doi: 10.1177/1933719109337038. Epub 2009 Jun 3.
Smoking during pregnancy has been shown to result in an increased risk of low birth weight. However, the mechanisms underlying this association are poorly understood. The insulin-like growth factor (IGF) system plays a critical role in the regulation of feto-placental growth and development, and abnormal processing of proIGF-II may alter its biological function. Our goal was to investigate the effects of exposure to nicotine on maternal, fetal, and neonatal IGF-II processing. Nulliparous female Wistar rats were randomly assigned to receive saline (vehicle) or nicotine bitartrate (1 mg x kg(-1) x d(- 1)). After mating, dams were euthanized at embryonic days 15, 18, and 21, and fetal body weight was recorded. Serum (fetal and maternal) was collected for determination of the IGF-II profile by Western blot analysis. Nicotine exposure prevented the decrease in maternal IGF-II processing seen in controls with advancing gestation. However, there was no influence of nicotine on fetal levels of IGF-II. Postnatally (postnatal day [PND] 21), pups exposed to nicotine in utero had decreased levels of big IGF-II. Our results show, for the first time, that nicotine exposure prevents the decrease of IGF-II processing in the maternal compartment. This may represent a compensatory mechanism allowing the mother to counteract the negative influence of nicotine on fetal growth and development. Our postnatal findings of suppressed IGF-II may help explain some of the long-term health complications seen in individuals exposed to smoking in utero.
孕期吸烟已被证明会增加低出生体重的风险。然而，这种关联背后的机制却知之甚少。胰岛素样生长因子（IGF）系统在胎儿-胎盘生长发育的调节中起着关键作用，前胰岛素样生长因子-II（proIGF-II）的异常加工可能会改变其生物学功能。我们的目标是研究尼古丁暴露对母体、胎儿和新生儿IGF-II加工的影响。将未生育的雌性Wistar大鼠随机分为两组，分别给予生理盐水（溶剂）或酒石酸尼古丁（1 mg·kg⁻¹·d⁻¹）。交配后，在胚胎第15、18和21天对母鼠实施安乐死，并记录胎儿体重。收集血清（胎儿和母体），通过蛋白质印迹分析测定IGF-II谱。尼古丁暴露可防止对照组中随着孕期进展母体IGF-II加工的减少。然而，尼古丁对胎儿IGF-II水平没有影响。出生后（出生后第21天），子宫内暴露于尼古丁的幼崽大IGF-II水平降低。我们的结果首次表明，尼古丁暴露可防止母体中IGF-II加工的减少。这可能代表一种补偿机制，使母亲能够抵消尼古丁对胎儿生长发育的负面影响。我们出生后的研究结果显示IGF-II受到抑制，这可能有助于解释子宫内暴露于吸烟环境的个体出现的一些长期健康并发症。
