Expression of the vascular endothelial growth factor receptor neuropilin-1 in the human endometrium

• Published in: Journal of reproductive immunology 2009-01, Vol.79 (2), p.129-136
• Main Authors: Hess, A.P, Schanz, A, Baston-Buest, D.M, Hirchenhain, J, Stoff-Khalili, M.A, Bielfeld, P, Kruessel, J.S
• Format: Article
• Language: English
• Subjects: Adult; Angiogenesis; Biological and medical sciences; Embryology: invertebrates and vertebrates. Teratology; Endometrium; Endometrium - metabolism; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - genetics; Humans; Immunohistochemistry; Menstrual cycle; Neuropilin-1; Neuropilin-1 - genetics; Neuropilin-1 - metabolism; Obstetrics and Gynecology; Receptors, Vascular Endothelial Growth Factor - metabolism; RNA, Messenger - genetics
• ISSN: 0165-0378; 1872-7603
• DOI: 10.1016/j.jri.2008.09.001

Abstract Angiogenesis is a key process in the endometrium which undergoes dramatic changes during the menstrual cycle. Molecules such as vascular endothelial growth factor (VEGF), acting via two tyrosine kinase family receptors (VEGFR1 [Flt-1] and VEGFR2 [KDR/Flk-1]), are potent modulators of angiogenesis and vascular remodelling in the endometrium. Recently, neuropilin-1 (NRP-1) was shown to be expressed in endothelial cells binding VEGF165 and therewith enhancing the binding of VEGF165 to VEGFR2. This suggests that NRP-1, in addition to the known VEGF receptors, may play an important role in VEGF-induced angiogenesis. In this study, the expression of NRP-1 in the cycling human endometrium has been investigated by reverse transcription (RT)-polymerase chain reaction (RT-PCR), semi-quantitative competitive RT-PCR (RT-cPCR) and immunohistochemical staining. NRP-1 was expressed in all 32 endometrium samples throughout the menstrual cycle. However, samples from the proliferative phase showed significantly higher expression levels of NRP-1 mRNA compared to samples from the secretory phase ( t / c -ratio 2.13 vs. 0.84, p < 0.05). Immunohistochemistry confirmed the results showing increased NRP-1 staining in vascular endothelium, glandular epithelium and stromal cells of the proliferative phase endometrium. This study demonstrates mRNA and protein expression of NRP-1 in human endometrium samples throughout the menstrual cycle. The enhanced expression of NRP-1 in the proliferative phase suggests that it may participate in hormonally regulated changes of endometrial angiogenesis, preparing the endometrium for the implantation of an embryo. NRP-1 expression might act as a co-factor for VEGF165 enhancing the angiogenic stimulus.