This Article Full Text Full Text (PDF) All Versions of this Article: 90/3/1783    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Germeyer, A. Articles by Nayak, N. R. Search for Related Content PubMed PubMed Citation Articles by Germeyer, A. Articles by Nayak, N. R. Related Collections Female Endocrinology

Cellular Expression and Hormonal Regulation of Neuropilin-1 and -2 Messenger Ribonucleic Acid in the Human and Rhesus Macaque Endometrium

Department of Gynecology and Obstetrics (A.G., A.E.H., L.C.G., N.R.N.), Stanford University, Stanford, California 94305; California National Primate Research Center (L.S.L., B.L.L.), University of California-Davis, Davis, California 95616; and Oregon National Primate Research Center (R.M.B.), Beaverton, Oregon 97006

Address all correspondence and requests for reprints to: Nihar R. Nayak, Ph.D., Department of Gynecology and Obstetrics, Stanford University School of Medicine, 300 Pasteur Drive, HH-333, Stanford, California 94305-5317. E-mail: nayakn{at}stanford.edu.

Although much is known about the biology of vascular endothelial growth factor (VEGF) and its cognate receptors (VEGFRs), VEGFR1 and VEGFR2, little is known about the roles of the VEGFRs neuropilin (NP)-1 and NP-2 in the primate endometrium. In this study, we investigated the cellular localization and hormonal regulation of NP-1 and NP-2 mRNA by in situ hybridization in the endometrium of ovariectomized, hormonally cycled rhesus macaques and women during the natural menstrual cycle. NP-1 mRNA was highly expressed in vascular endothelium and in stromal cells, but in these cells, NP-1 expression did not change during the menstrual cycle. However, NP-1 mRNA was also expressed in the luminal epithelium (not the glands), and its expression in these cells was elevated during the mid- to late proliferative phase and completely suppressed during the secretory phase. The increase in NP-1 level in the luminal epithelium was estradiol dependent because such expression was not detectable in the absence of estradiol in ovariectomized, hormone-deprived animals. Moreover, NP-1 expression in the luminal epithelium was highly correlated with the degree of proliferation in these cells. A recent study showed that blockade of VEGF action can inhibit luminal epithelial cell proliferation, but there is no evidence of VEGFR1 and VEGFR2 expression in these cells. Therefore, NP-1 may be the relevant VEGFR that mediates proliferation in this epithelium. NP-2 mRNA, unlike NP-1, was expressed only by the endothelium of veins, and in these cells, its expression was hormonally regulated in the converse manner: it was very low during the proliferative phase and high during the secretory phase. The increased permeability and edema observed during the secretory phase in the primate endometrium may be mediated in part by VEGF-NP-2 interaction. In the human endometrium, the pattern of expression and cellular localization of both NP-1 and NP-2 during the menstrual cycle were essentially identical with that seen in the rhesus macaque endometrium. These are the first data to specify the hormonal regulation and cell-specific expression of NP-1 and NP-2 mRNA in the endometrium of both women and nonhuman primates. The findings extend our understanding of VEGF action in the primate endometrium.

This article has been cited by other articles:

				T. Strowitzki, A. Germeyer, R. Popovici, and M. von Wolff The human endometrium as a fertility-determining factor Hum. Reprod. Update, September 1, 2006; 12(5): 617 - 630. [Abstract] [Full Text] [PDF]

				C. Punyadeera, V.L. Thijssen, S. Tchaikovski, R. Kamps, B. Delvoux, G.A.J. Dunselman, A.F.P.M. de Goeij, A.W. Griffioen, and P.G. Groothuis Expression and regulation of vascular endothelial growth factor ligands and receptors during menstruation and post-menstrual repair of human endometrium Mol. Hum. Reprod., June 1, 2006; 12(6): 367 - 375. [Abstract] [Full Text] [PDF]

				N. R. Nayak, C. J. Kuo, T. A. Desai, S. J. Wiegand, B. L. Lasley, L. C. Giudice, and R. M. Brenner Expression, localization and hormonal control of angiopoietin-1 in the rhesus macaque endometrium: potential role in spiral artery growth Mol. Hum. Reprod., November 1, 2005; 11(11): 791 - 799. [Abstract] [Full Text] [PDF]