Developmental regulation of vascular endothelial growth/permeability factor messenger ribonucleic acid levels in and vascularization of the villous placenta during baboon pregnancy.
Developmental regulation of vascular endothelial growth/permeability factor messenger ribonucleic acid levels in and vascularization of the villous placenta during baboon pregnancy.
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DOI：
10.1210/endo.142.5.8174
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发表时间：
2001-05
期刊：
影响因子：
4.8
通讯作者：
Victoria A. Hildebrandt;J. Babischkin;R. D. Koos;G. Pepe;E. Albrecht
中科院分区：
文献类型：
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作者：
Victoria A. Hildebrandt;J. Babischkin;R. D. Koos;G. Pepe;E. Albrecht
血管内皮生长/通透因子（VEG/PF）在血管生成中发挥重要作用；然而，对于人类妊娠期间 VEG/PF 和胎盘内血管系统的发育调节知之甚少。因此，在本研究中，在狒狒身上采用了发育方法来确定 VEG/PF 及其 fms 样酪氨酸激酶 (flt-1) 和包含激酶插入结构域 (KDR/flk-1) 受体的胎盘来源，以及随着妊娠进展雌激素的增加是否与胎盘 VEG/PF 表达和血管化的相应增加有关。 VEG/PF 信使 RNA (mRNA) 水平通过竞争性 RT-PCR 测定狒狒妊娠（足月 = 184 天）第 45 天和 54 天（早期）、60 天（早期）、100 天（中期）和 165-170 天（晚期）胎盘中通过 Percoll 梯度离心分离的绒毛细胞组分中的 VEG/PF 信使 RNA (mRNA) 水平。母体外周血清雌二醇从妊娠早期的极低浓度（0.15-0.20 ng/ml）增加到第 60-85 天的早期峰值超过 2.5 ng/ml，并在狒狒怀孕后期达到 4-6 ng/ml 的峰值水平。 VEG/PF mRNA 在合体滋养层中低水平表达（<2,000 attomol/μg 总 RNA），并且该部分的值不会随着妊娠的进展而发生显着变化。 VEG/PF mRNA 表达在内绒毛核心细胞部分稍高；然而，在妊娠早期和晚期，该水平下降（P < 0.05）。细胞滋养层是 VEG/PF mRNA 的主要来源，其水平从第 45 天的 3,631 +/- 844 attomol/μg 总 RNA 增加到第 170 天的 25,807 +/- 5,873 attomol/μg 总 RNA。通过免疫细胞化学测定的 VEG/PF 蛋白表达在细胞滋养层中丰富，而在合体滋养层中较低。和内部绒毛核心细胞。 flt-1 和 KDR/flk-1 受体在狒狒绒毛胎盘的血管内皮细胞中表达。通过图像分析确定，绒毛胎盘被血管占据的百分比和血管数量/mm(2)绒毛组织逐渐增加（P < 0.001；r = 0.97），分别从第54天的3.4 +/- 0.2%和447 +/- 29增加到第54天的15.9 +/- 0.9%和1,375 +/- 71。 170. 总之，本研究表明，绒毛细胞滋养细胞是狒狒绒毛胎盘中 VEG/PF mRNA 和蛋白质的主要来源，并且细胞滋养细胞 VEG/PF mRNA 水平和绒毛胎盘的血管化与妊娠晚期雌二醇浓度的增加密切相关。这些结果与以下概念一致：雌激素在灵长类动物妊娠期间发育中的胎盘内建立新的血管系统中具有重要作用，并且 VEG/PF 介导这一过程。
Vascular endothelial growth/permeability factor (VEG/PF) has an important role in angiogenesis; however, very little is known about the developmental regulation of VEG/PF and the vascular system within the placenta during human pregnancy. In the present study, therefore, a developmental approach was used in the baboon to determine the placental source of VEG/PF and its fms-like tyrosine kinase (flt-1) and kinase-insert domain containing (KDR/flk-1) receptors, and whether the rise in estrogen with advancing pregnancy was associated with a corresponding increase in placental VEG/PF expression and vascularization. VEG/PF messenger RNA (mRNA) levels were determined by competitive RT-PCR in villous cell fractions isolated by Percoll gradient centrifugation from placentas obtained on days 45 and 54 (very early), 60 (early), 100 (mid), and 165-170 (late) of baboon pregnancy (term = 184 days). Maternal peripheral serum estradiol increased from very low concentrations early in gestation (0.15-0.20 ng/ml) to an early surge of over 2.5 ng/ml on days 60-85, and peak levels of 4-6 ng/ml late in baboon pregnancy. VEG/PF mRNA was expressed in low level in the syncytiotrophoblast (<2,000 attomol/microgram total RNA), and values in this fraction did not change significantly with advancing gestation. VEG/PF mRNA expression was slightly greater in the inner villous core cell fraction; however, levels decreased (P < 0.05) between early and late gestation. Cytotrophoblasts were a major source of VEG/PF mRNA and levels increased (P < 0.01) from 3,631 +/- 844 attomol/microgram total RNA on day 45 to 25,807 +/- 5,873 attomol/microgram total RNA on day 170. VEG/PF protein expression determined by immunocytochemistry was abundant in cytotrophoblasts and lower in the syncytiotrophoblast and inner villous core cells. The flt-1 and KDR/flk-1 receptors were expressed in the vascular endothelial cells of the baboon villous placenta. The percentage of villous placenta occupied by blood vessels and the number of vessels/mm(2) villous tissue, determined by image analysis, progressively increased (P < 0.001; r = 0.97) from 3.4 +/- 0.2% and 447 +/- 29, respectively, on day 54 to 15.9 +/- 0.9% and 1,375 +/- 71, respectively, on day 170. In summary, the present study shows that villous cytotrophoblasts were a major source of VEG/PF mRNA and protein in the baboon villous placenta, and that cytotrophoblast VEG/PF mRNA levels and vascularization of the villous placenta closely paralleled the increase in estradiol concentrations of advancing pregnancy. These results are consistent with the concept that estrogen has an important role in establishing the new vascular system within the developing placenta during primate pregnancy and that VEG/PF mediates this process.