Maternal and Fetal Health Research Centre, University of Manchester, St. Mary's Hospital, Oxford Road, Manchester M13 9WL, United Kingdom.
J Clin Endocrinol Metab. 2012 Nov;97(11):E2098-104. doi: 10.1210/jc.2012-1679. Epub 2012 Sep 4.
Discrete regulation of the uterine and placental vasculatures is an important feature of uteroplacental perfusion and pregnancy success because appropriate maternal/fetal exchange of nutrients and gases is crucial for normal fetal growth. Placental vasculature lacks autonomic innervation so tone is controlled by locally derived vasoactive factors. IGF-I, which is produced by the placenta, is critical for normal fetal growth and studies of animal vascular systems have shown that IGF-I regulates vasomotor tone.
The objective of the study was to determine whether IGF-I directly alters human placental and myometrial arterial tone in vitro.
Women with uncomplicated pregnancy delivering a singleton infant at term participated in the study.
The study was conducted at university hospital laboratories.
MAIN OUTCOME MEASURE(S): Comparison of arterial tension measured before and after exposure to IGF-I.
Placental and myometrial arteries were mounted on a wire myograph, exposed to the constrictor U46619 (10(-10) to 10(-5) m), returned to baseline tension, and then incubated with IGF-I (0-500 ng/ml) for various time points before performing a second dose-response curve to U46619. IGF-I receptor protein expression was assessed.
IGF-I did not acutely alter the response of placental arteries to U46619. Exposure of myometrial arteries to IGF-I caused a rightward shift of U46619 dose-response curves (P < 0.05); EC(50) data were significantly increased at 30 (15.5 ± 2.8 vs. 133 ± 44 nm, before and after IGF treatment, respectively) and 60 min (10.9 ± 1.9 vs. 146 ± 47 nm). Placental and myometrial arteries had a similar IGF-I receptor expression profile.
IGF-I acutely modulates the vasomotor tone of human myometrial, but not placental, arteries, suggesting that IGF-I regulates the delivery of maternal blood to the placenta.
子宫和胎盘血管的离散调节是胎盘灌注和妊娠成功的重要特征,因为适当的母婴/胎儿营养和气体交换对于正常的胎儿生长至关重要。胎盘血管缺乏自主神经支配,因此张力由局部来源的血管活性因子控制。IGF-I 由胎盘产生,对正常胎儿生长至关重要,动物血管系统的研究表明 IGF-I 调节血管舒缩张力。
本研究旨在确定 IGF-I 是否直接改变体外人胎盘和子宫动脉的张力。
参加研究的是患有单胎足月妊娠的无并发症孕妇。
该研究在大学医院实验室进行。
比较 IGF-I 暴露前后动脉张力的变化。
胎盘和子宫动脉被安装在一个金属丝肌动描记器上,暴露于缩血管物质 U46619(10(-10)至 10(-5)m),恢复基线张力,然后用 IGF-I(0-500ng/ml)孵育不同时间点,然后再进行第二次 U46619 剂量反应曲线。评估 IGF-I 受体蛋白表达。
IGF-I 并未急性改变胎盘动脉对 U46619 的反应。子宫动脉暴露于 IGF-I 导致 U46619 剂量反应曲线右移(P <0.05);30 分钟(15.5 ± 2.8 与 133 ± 44nm,IGF 处理前后)和 60 分钟(10.9 ± 1.9 与 146 ± 47nm)时 EC50 数据显著增加。胎盘和子宫动脉具有相似的 IGF-I 受体表达谱。
IGF-I 急性调节人子宫动脉的血管舒缩张力,但不调节胎盘动脉的张力,提示 IGF-I 调节母体血液向胎盘的输送。