Up-regulation of endocrine gland-derived vascular endothelial growth factor but not vascular endothelial growth factor in human ectopic endometriotic tissue

Abstract

To study the expression of vascular endothelial growth factor (VEGF), endocrine gland-derived VEGF (EG-VEGF/PK1), and its receptors (PKR1 and PKR2) in eutopic and ectopic endometrial tissues. A case-control study. University reproduction unit. Infertile women undergoing diagnostic laparoscopy for tubal patency. Endometrial and endometriotic tissue sampling from women with and without endometriosis. Quantitative polymerase chain reaction (PCR) analysis of genes in eutopic and ectopic endometrial tissues. The EG-VEGF protein was studied by immunohistochemistry. In normal endometrium, EG-VEGF messenger RNA (mRNA) expression was 50-fold higher in the secretory than in the proliferative phase, but that of PKR1 was 6-fold higher in the latter than in the former. The PKR2 transcript was detected in the proliferative but not the secretory endometrium. In patients with endometriosis, eutopic endometrial PKR2 transcript level was 4-fold higher in the proliferative than in the secretory phase. No differences in EG-VEGF or PKR1 were found in proliferative versus secretory endometrium in these patients. There were no significant differences in the expression of EG-VEGF in eutopic endometrium of normal women and in those with endometriosis. In the paired laser-captured microdissected eutopic endometrial and ectopic endometriotic samples, a significantly higher EG-VEGF, but not VEGF, transcript level was detected in the ectopic when compared with eutopic samples; whereas the expressions of PKR1 and PKR2 were barely detectable. The H-scoring confirmed that the stroma of endometriotic samples had a significantly higher EG-VEGF protein expression than that in the paired eutopic endometrium. High levels of EG-VEGF expression may play an important role in angiogenesis in endometriotic tissues.