Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-13T01:57:15.931Z Has data issue: false hasContentIssue false
  • English
  • Français

The corpora lutea proangiogenic state of VEGF system components is turned to antiangiogenic at the later phase of the oestrous cycle in cows

Published online by Cambridge University Press:  17 September 2014

A. Guzmán ,
R. Macías-Valencia ,
F. Fierro-Fierro ,
C. G. Gutiérrez  and
A. M. Rosales-Torres
A. Guzmán
Affiliation:
Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, CP 04960, México D.F., México
R. Macías-Valencia
Affiliation:
Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, CP 04960, México D.F., México
F. Fierro-Fierro
Affiliation:
Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, CP 09340, México D.F., México
C. G. Gutiérrez
Affiliation:
Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Avenida Universidad 3000, CP 04510, México D.F., México
A. M. Rosales-Torres*
Affiliation:
Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, CP 04960, México D.F., México
*
†E-mail: anamaria@correo.xoc.uam.mx
Get access

Abstract

Blood vessel expansion and reduction in the corpus luteum (CL) is regulated by the vascular endothelial growth factor (VEGF) system and linked to the maintenance of the CL. The VEGF system has both angiogenic and antiangiogenic ligands and receptors. Our objective was to evaluate the relationship between the mRNA expression of angiogenic and antiangiogenic members of the VEGF system in the CL, throughout the luteal phase of the oestrous cycle in cows. The CL of 18 cows were collected by transvaginal surgery on days 4, 6, 9, 12, 15 and 18 of the oestrous cycle and the mRNA expression of VEGF system components was evaluated by quantitative real-time PCR. The mRNA expression of VEGF ligands and receptors increased (P<0.05) from the early- and mid-luteal phase (days 4 to 12) reaching its maximum expression on day 15 of the cycle. We found no expression of VEGF164b throughout the cycle. Expression of sVEGFR1 did not change during the oestrous cycle and exceeded that of the VEGFR1 by 100 times. Nonetheless, as VEGFR1 increased, the relationship between the soluble and membrane receptor decreased (P<0.01). In contrast, the expression of VEGFR2 was higher than that of its soluble isoform for all days studied, however, the ratio between the membrane-bound and its soluble counterpart decreased continuously throughout the cycle (P<0.01). Our results show that the expression levels for VEGF ligands, receptors and their antagonistic counterparts are adjusted during CL development and regression, to upregulate angiogenesis early in the oestrous cycle and restrict it at the time of luteolysis.

Keywords

corpus luteumdevelopmentluteolysisVEGF systembovine
Type
Research Article
Information
animal , Volume 9 , Supplement 2 , February 2015 , pp. 301 - 307
Copyright
© The Animal Consortium 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Berisha, B, Schams, D, Kosmann, M, Amselgruber, W and Einspanier, R 2000. Expression and tissue concentration of vascular endothelial growth factor, its receptors, and localization in the bovine corpus luteum during estrous cycle and pregnancy. Biology of Reproduction 63, 1106–1114.Google Scholar
Boonyaprakob, U, Gadsby, JE, Hedgpeth, V, Routh, P and Almond, GW 2003. Expression and localization of vascular endothelial growth factor and its receptors in pig corpora lutea during the oestrous cycle. Reproduction 126, 393–405.CrossRefGoogle ScholarPubMed
Chomczynski, P and Sacchi, N 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analytical Biochemistry 162, 156–159.Google Scholar
Crossin, KL 2012. Oxygen levels and the regulation of cell adhesion in the nervous system: a control point for morphogenesis in development, disease and evolution? Cell Adhesion & Migration 6, 49–58.Google Scholar
Ferrara, N 2004. Vascular endothelial growth factor: basic science and clinical progress. Endocrine Reviews 25, 581–611.CrossRefGoogle ScholarPubMed
Fraser, HM and Wulff, C 2003. Angiogenesis in the corpus luteum. Reproductive Biology and Endocrinology 1, 1–8.Google Scholar
Fraser, HM, Wilson, H, Morris, KD, Swanston, I and Wiegand, SJ 2005. Vascular endothelial growth factor Trap suppresses ovarian function at all stages of the luteal phase in the macaque. The Journal of Clinical Endocrinology and Metabolism 90, 5811–5818.CrossRefGoogle ScholarPubMed
Fraser, HM, Wilson, H, Wulff, C, Rudge, JS and Wiegand, SJ 2006. Administration of vascular endothelial growth factor Trap during the ‘post-angiogenic’ period of the luteal phase causes rapid functional luteolysis and selective endothelial cell death in the marmoset. Reproduction 132, 589–600.Google Scholar
Ginther, OJ, Shrestha, HK, Fuenzalida, MJ, Shahiduzzaman, AK, Hannan, MA and Beg, MA 2010. Intrapulse temporality between pulses of a metabolite of prostaglandin F 2α and circulating concentrations of progesterone before, during, and after spontaneous luteolysis in heifers. Theriogenology 74, 1179–1186.CrossRefGoogle ScholarPubMed
Harper, SJ and Bates, DO 2008. VEGF-A splicing: the key to anti-angiogenic therapeutics? Nature Reviews Cancer 8, 880–887.Google Scholar
Kaczmarek, M, Schams, D and Ziecik, A 2005. Role of vascular endothelial growth factor in ovarian physiology – an overview. Reproductive Biology 5, 111–136.Google ScholarPubMed
Kaczmarek, M, Kiewisz, J, Schams, D and Ziecik, AJ 2009. Expression of VEGF-receptor system in conceptus during peri-implantation period and endometrial and luteal expression of soluble VEGFR-1 in the pig. Theriogenology 71, 1298–1306.Google Scholar
Kremer, C, Breier, G, Risau, W and Plate, KH 1997. Up-regulation of flk-1/vascular endothelial growth factor receptor 2 by its ligand in a cerebral slice culture system. Cancer Research 57, 3852–3859.Google Scholar
Macias, VR, Pinzón, C, Fierro, F, Vergara, M, Martínez, D, Rosado, A, Gutiérrez, CG and Rosales-Torres, AM 2012. Identification of soluble forms of vascular endothelial growth factor receptors, sVEGFR-1 and sVEGFR-2, in bovine dominant follicles. Reproduction in Domestic Animals 3, 39–42.Google Scholar
Maybin, JA, Hirani, N, Brown, P, Jabbour, HN and Critchley, HO 2011. The regulation of vascular endothelial growth factor by hypoxia and prostaglandin F2α during human endometrial repair. The Journal of Clinical Endocrinology and Metabolism 96, 2475–2483.CrossRefGoogle ScholarPubMed
Nett, TM, McClellan, MC and Niswender, GD 1976. Effects of prostaglandins on the ovine corpus luteum: blood flow, secretion of progesterone and morphology. Biology of Reproduction 15, 66–78.Google Scholar
Nishimura, R and Okuda, K 2010. Hypoxia is important for establishing vascularization during corpus luteum formation in cattle. The Journal of Reproduction and Development 56, 110–116.Google Scholar
Nowak, DG, Woolard, J, Amin, EM, Konopatskaya, O, Saleem, MA, Churchill, AJ, Ladomery, MR, Harper, SJ and Bates, DO 2008. Expression of pro- and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factors. Journal of Cell Science 15, 3487–3495.CrossRefGoogle Scholar
Owen, LA, Uehara, H, Cahoon, J, Huang, W, Simonis, J and Ambati, BK 2012. Morpholino-mediated increase in soluble Flt-1 expression results in decreased ocular and tumor neovascularization. PLoS One 7, e33576.CrossRefGoogle ScholarPubMed
Qiu, Y, Seager, M, Osman, A, Castle-Miller, J, Bevan, H, Tortonese, DJ, Murphy, D, Harper, SJ, Fraser, HM, Donaldson, LF and Bates, DO 2012. Ovarian VEGF(165)b expression regulates follicular development, corpus luteum function and fertility. Reproduction 143, 501–511.Google Scholar
Rangel, PL, Rodríguez, A, Rojas, S, Sharp, PJ and Gutierrez, CG 2009. Testosterone stimulates progesterone production and STAR, P450 cholesterol side-chain cleavage and LH receptor mRNAs expression in hen (Gallus domesticus) granulosa cells. Reproduction 138, 961–969.Google Scholar
Redmer, DA, Dai, Y, Li, J, Charnock-Jones, DS, Smith, SK, Reynolds, LP and Moor, RM 1996. Characterization and expression of vascular endothelial growth factor (VEGF) in the ovine corpus luteum. Journal of Reproduction and Fertility 108, 157–165.CrossRefGoogle ScholarPubMed
Rennel, ES, Varey, AH, Churchill, AJ, Wheatley, ER, Stewart, L, Mather, S, Bates, DO and Harper, SJ 2009. VEGF(121)b, a new member of the VEGF(xxx)b family of VEGF-A splice isoforms, inhibits neovascularisation and tumour growth in vivo. British Journal of Cancer 6, 1183–1193.Google Scholar
Ribeiro, L, Bacci, ML, Seren, E, Tamanini, C and Forni, M 2007. Characterization and differential expression of vascular endothelial growth factor isoforms and receptors in swine corpus luteum throughout estrous cycle. Molecular Reproduction and Development 74, 163–171.Google Scholar
Roda, JM, Sumner, LA, Evans, R, Phillips, GS, Marsh, CB and Eubank, TD 2011. Hypoxia-inducible factor-2α regulates GM-CSF-derived soluble vascular endothelial growth factor receptor 1 production from macrophages and inhibits tumor growth and angiogenesis. Journal of Immunology 187, 1970–1976.CrossRefGoogle ScholarPubMed
Shirasuna, K, Nitta, A, Sineenard, J, Shimizu, T, Bollwein, H and Miyamoto, A 2012. Vascular and immune regulation of corpus luteum development, maintenance, and regression in the cow. Domestic Animal Endocrinology 43, 198–211.CrossRefGoogle ScholarPubMed
Szentirmai, O, Baker, CH, Bullain, SS, Lin, N, Takahashi, M, Folkman, J, Mulligan, RC and Carter, BS 2008. Successful inhibition of intracranial human glioblastoma multiforme xenograft growth via systemic adenoviral delivery of soluble endostatin and soluble vascular endothelial growth factor receptor-2: laboratory investigation. Journal of Neurosurgery 108, 979–988.Google Scholar
Tamanini, C and Ambrogi De, M 2004. Angiogenesis in developing follicle and corpus luteum. Reproduction in Domestic Animals 4, 206–216.CrossRefGoogle Scholar
Tricarico, C, Pinzani, P, Bianchi, S, Paglierani, M, Distante, V, Pazzagli, M, Bustin, SA and Orlando, C 2002. Quantitative real-time reverse transcription polymerase chain reaction: normalization to rRNA or single housekeeping genes is inappropriate for human tissue biopsies. Analytical Biochemistry 309, 293–300.CrossRefGoogle ScholarPubMed
Vonnahme, KA, Redmer, DA, Borowczyk, E, Bilski, JJ, Luther, JS, Johnson, ML, Reynolds, LP and Grazul-Bilska, AT 2006. Vascular composition, apoptosis, and expression of angiogenic factors in the corpus luteum during prostaglandin F2-alpha-induced regression in sheep. Reproduction 131, 1115–1126.Google Scholar
Waltenberger, J, Claesson-Welsh, L, Siegbahn, A, Shibuya, M and Heldin, CH 1994. Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. The Journal of Biological Chemistry 28, 26988–26995.Google Scholar
Wang, D, Donner, DB and Warren, RS 2000. Homeostatic modulation of cell surface KDR and Flt1 expression and expression of the vascular endothelial cell growth factor (VEGF) receptor mRNAs by VEGF. The Journal of Biological Chemistry 275, 15905–15911.Google Scholar
Wang, R, Zhang, XW, Wang, GQ, Chen, XC, Tian, L, Yang, HS, Hu, M, Peng, F, Yang, JL, He, QM, Zhang, W, Jiang, Y, Deng, HX, Wen, YJ, Li, J, Zhao, X and Wei, YQ 2006. Systemic inhibition of tumor growth by soluble Flk-1 gene therapy combined with cisplatin. Cancer Gene Therapy 13, 940–947.Google Scholar
Zeng, H, Dvorak, HF and Mukhopadhyay, D 2001. Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) peceptor-1 down-modulates VPF/VEGF receptor-2-mediated endothelial cell proliferation, but not migration, through phosphatidylinositol 3-kinase-dependent pathways. The Journal of Biological Chemistry 20, 26969–26979.Google Scholar
Supplementary material: File

Guzmán Supplementary Material

Table S1

Download Guzmán Supplementary Material(File)
File 101.9 KB