Expression of vascular endothelial growth/permeability factor by endometrial glandular epithelial and stromal cells in baboons during the menstrual cycle and after ovariectomy.
Expression of vascular endothelial growth/permeability factor by endometrial glandular epithelial and stromal cells in baboons during the menstrual cycle and after ovariectomy.
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DOI：
10.1210/en.2002-220385
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发表时间：
2002-10
期刊：
影响因子：
4.8
通讯作者：
A. Niklaus;J. Babischkin;G. Aberdeen;G. Pepe;E. Albrecht
中科院分区：
文献类型：
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作者：
A. Niklaus;J. Babischkin;G. Aberdeen;G. Pepe;E. Albrecht
血管内皮生长/渗透因子（VEG/PF）在血管生成中起着至关重要的作用，而新生血管形成是子宫内膜准备植入的关键。然而，VEG/PF合成的调节在人类月经周期期间子宫内膜的特定细胞类型还没有得到很好的理解。因此，在本研究中，狒狒被用作非人灵长类动物，以确定卵巢在体内子宫内膜VEG/PF表达中的作用。VEG/PF mRNA水平进行了定量竞争性RT-PCR在整个子宫内膜和腺上皮细胞和基质细胞分离的子宫内膜激光捕获显微切割狒狒在正常月经周期和卵巢切除术后，血清雌二醇和孕酮下降到检测不到的水平。在整个子宫内膜中，323 bp VEG/PF mRNA产物的平均（+/-SE）水平（阿托摩尔/微克总RNA）反映了所有VEG/PF亚型的集体表达，在卵泡中期和晚期分别为785和727 +/- 158，在血清雌二醇的中期高峰期为1108 +/- 320。VEG/PF mRNA水平随后短暂下降，然后在月经周期的黄体晚期增加到1029 +/- 365阿托摩尔/微克RNA。VEG/PF mRNA水平（每毫微微摩尔18 S rRNA的阿托摩尔数）在月经周期的中期雌二醇峰值和中期黄体期的腺上皮（2.27 +/- 1.11）和基质（2.54 +/- 0.70）细胞中相似（分别为2.34 +/- 1.30和1.49 +/- 0.53）。VEG/PF蛋白在腺上皮、腔上皮、间质和血管内皮中表达丰富。子宫内膜血管密度和百分比血管化面积，由形态测量图像分析，在狒狒月经周期的各个阶段是相似的。卵巢切除术后，VEG/PF mRNA水平（每毫微微摩尔18 S rRNA的阿托摩尔数）在子宫内膜腺体（0.52 +/- 0.21）和基质（0.22 +/- 0.11）中分别下降到约20%和10%（P < 0.05），在完整的狒狒在中期周期雌激素激增。此外，有相对较少的VEG/PF蛋白免疫染色在子宫内膜腺体，间质和血管内皮卵巢切除术后。总之，卵巢切除术后腺上皮和基质细胞中VEG/PF mRNA和蛋白表达明显受到抑制，表明这些子宫内膜细胞中这种血管生成因子的合成依赖于卵巢分泌的产物。此外，子宫内膜VEG/PF表达保持相对恒定，因此可作为整个月经周期的血管生成系统的一个组成部分，大概是逐步促进子宫内膜的血管重建。
Vascular endothelial growth/permeability factor (VEG/PF) has a crucial role in angiogenesis, and neovascularization is essential in preparing the uterine endometrium for implantation. However, the regulation of VEG/PF synthesis by particular cell types of the endometrium during the human menstrual cycle is not well understood. Therefore, in the present study the baboon was used as a nonhuman primate to determine the role of the ovary in vivo in endometrial VEG/PF expression. VEG/PF mRNA levels were quantified by competitive RT-PCR in whole uterine endometrium and in glandular epithelial and stromal cells isolated from the endometrium by laser capture microdissection of baboons during the normal menstrual cycle and after ovariectomy, which decreased serum estradiol and progesterone to undetectable levels. Mean (+/-SE) levels (attomoles per micrograms of total RNA) of the 323-bp VEG/PF mRNA product, which reflected collective expression of all VEG/PF isoforms, in whole endometrium were 785 and 727 +/- 158 during the mid and late follicular phases, respectively, and 1108 +/- 320 during the midcycle surge in serum estradiol. VEG/PF mRNA levels then declined briefly before increasing to 1029 +/- 365 attomoles/ micro g RNA during the late luteal phase of the menstrual cycle. VEG/PF mRNA levels (attomoles per femtomole of 18S rRNA) were similar in glandular epithelial (2.27 +/- 1.11) and stromal (2.54 +/- 0.70) cells at the midcycle estradiol peak and the midluteal phase of the menstrual cycle (2.34 +/- 1.30 and 1.49 +/- 0.53, respectively). Immunocytochemical expression of VEG/PF protein was abundant in glandular and luminal epithelium, stroma, and vascular endothelium. Endometrial vessel density and percent vascularized area, determined by morphometric image analysis, were similar during the various stages of the baboon menstrual cycle. After ovariectomy, VEG/PF mRNA levels (attomoles per femtomole of 18S rRNA) in the endometrial glands (0.52 +/- 0.21) and stroma (0.22 +/- 0.11) were decreased to values that were approximately 20% and 10% (P < 0.05), respectively, of those in intact baboons during the midcycle estrogen surge. Moreover, there was relatively little VEG/PF protein immunostaining in the endometrial glands, stroma, and vascular endothelium after ovariectomy. In summary, VEG/PF mRNA and protein expression in glandular epithelial and stromal cells were markedly suppressed after ovariectomy, indicating that synthesis of this angiogenic factor in these endometrial cells is dependent upon a product(s) secreted by the ovary. Moreover, endometrial VEG/PF expression remained relatively constant and thus was available as a component of the angiogenic system throughout the menstrual cycle, presumably to progressively promote vascular reconstruction of the endometrium.