Hemodynamic, vascular, and reproductive impact of FMS-like tyrosine kinase 1 (FLT1) blockade on the uteroplacental circulation during normal mouse pregnancy.
Hemodynamic, vascular, and reproductive impact of FMS-like tyrosine kinase 1 (FLT1) blockade on the uteroplacental circulation during normal mouse pregnancy.
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FMS 样酪氨酸激酶 1 (FLT1) 阻断对正常小鼠妊娠期间子宫胎盘循环的血流动力学、血管和生殖影响。
DOI：
10.1095/biolreprod.111.095380
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发表时间：
2012
影响因子：
3.6
通讯作者：
Osol,George
中科院分区：
文献类型：
--
作者：
Khankin,EliyahuV;Mandala,Maurizio;Colton,Ilsley;Karumanchi,SAnanth;Osol,George
为了研究fms样酪氨酸激酶1 （FLT1，也称为VEGFR1）信号在妊娠期间的作用，从妊娠第8天或第12天开始给小鼠注射抗FLT1中和抗体（Ab），此后每隔一天注射一次，直到第18天；仅注射小鼠作为对照。第13、18天采用超声测量子宫动脉血流，第19天采用形态测量法测量子宫拱廊血管重构情况；通过测定产仔数、吸收率、幼犬和胎盘重量来评估繁殖性能。在第8天或第12天开始注射Ab可导致第13天和第18天子宫动脉收缩和舒张峰值血流显著降低。此外，正常的生殖功能受到损害，如平均存活幼崽数量显著减少以及吸收率提高所证明的那样。这一组的生殖能力也受到了显著的影响，尽管不那么严重。没有证据表明子宫主动脉直径减少，但动脉扩张性降低，子宫主静脉直径明显缩小。子宫主动脉和节段动脉长度也明显减少。各组胎盘和幼犬体重相近。小鼠妊娠期间FLT1抑制会损害胎儿-胎盘单位的血流量，损害血管重塑的几个指标，降低繁殖力，增加胎儿的再吸收。在妊娠早期，FLT1抑制的效果最为明显。
To investigate the role of FMS-like tyrosine kinase 1 (FLT1, also known as VEGFR1) signaling during pregnancy, mice were injected with anti-FLT1 neutralizing antibody (Ab) beginning on Gestational Day 8 or 12 and every other day thereafter until Day 18; vehicle-only injected mice served as controls. Uterine artery blood flow was measured with ultrasound on Days 13 and 18, and morphometric measurements of the uterine arcade were carried out on Day 19 to provide a measure of gestational vascular remodeling; reproductive performance was evaluated by determining litter size, resorption rates, and pup and placental weights. Ab injections beginning on Day 8 or Day 12 resulted in significant reductions of uterine artery peak systolic and diastolic flows at Days 13 and 18. In addition, normal reproductive function was compromised, as evidenced by a significant reduction in average number of viable pups along with enhanced resorption rates. Reproductive performance was also significantly compromised in this group, although less severely. There was no evidence of a reduction in main uterine artery diameters, though arterial distensibility was reduced, and the diameter of the main uterine vein was significantly smaller in the Ab-injected mice. Significant reductions in main uterine artery and segmental artery length were also noted. Placental and pup weights were similar in all the groups. FLT1 inhibition during murine pregnancy impaired blood flow to the fetal-placental unit, compromised several indices of vascular remodeling, reduced fecundity, and increased fetal reabsorptions. The effects of FLT1 inhibition are most pronounced when targeted during early pregnancy.