Skip to main content
×
×
Home

Importance of vascular endothelial growth factor (VEGF) in ovarian physiology of mammals

  • Valdevane Rocha Araújo (a1), Ana Beatriz Graça Duarte (a2), Jamily Bezerra Bruno (a2), Cláudio Afonso Pinho Lopes (a2) and José Ricardo de Figueiredo (a2)...
Summary

Ovarian folliculogenesis in mammals is a complex process. Several compounds have been tested during in vitro culture of follicular cells for a better understanding of the mechanisms and factors related to ovarian folliculogenesis in mammals. From these compounds, vascular endothelial growth factor (VEGF) can be highlighted, as it is strongly associated with angiogenesis and, in recent years, its presence in ovarian cells has been investigated extensively. Previous studies have shown that the presence of VEGF protein, as well as mRNA expression of its receptor 2 (VEGFR-2) increases during follicular development. Therefore, it is likely that the interaction between VEGF and VEGFR-2 is crucial to promote follicular development. However, few studies on the influence of this factor on follicular development have been reported. This review addresses aspects related to the structural characterization and mechanism of action of VEGF and its receptors, and their biological importance in the ovary of mammals.

Copyright
Corresponding author
All correspondence to: Universidade Estadual do Ceará (UECE), Faculdade de Veterinária (FAVET), Programa de Pós-Graduação em Ciências Veterinárias (PPGCV), Laboratório de Manipulação de Oócitos e Folículos Pré-Antrais (LAMOFOPA), Av. Paranjana, 1700, Campus do Itaperi, Fortaleza–CE–Brasil, CEP: 60740–930Brasil. Tel: +55 85 3101 9852. Fax: +55 85 3101 9840. e-mail: val_exclusiva@yahoo.com.br
References
Hide All
Abir, R., Ao, A., Zhang, X.Y., Garor, R., Nitke, S. & Fisch, B. (2010). Vascular endothelial growth factor A and its two receptors in human preantral follicles from fetuses, girls, and women. Fertil. Steril. 93, 2337–47.
Alon, T., Hemo, I., Itin, A., Pe'er, J., Stone, J. & Keshet, E. (1995). Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat. Med. 1, 1024–8.
Al-zi'abi, M.O., Watson, E.D. & Fraser, H.M. (2003). Angiogenesis and vascular endothelial growth factor expressions in the equine corpus luteum. Reproduction 125, 259–70.
Barboni, B., Turriani, M., Galeati, G., Spinaci, M., Bacci, M.L., Forni, M. & Mattioli, M. (2000). Vascular endothelial growth factor production in growing pig antral follicles. Biol. Reprod. 63, 858–64.
Bates, D.O & Curry, F.E. (1997). Vascular endothelial growth factor increases microvascular permeability via a Ca2+-dependent pathway. Am. J. Physiol. 273, H68794.
Bates, D.O., Cui, T.G., Doughty, J.M., Winkler, M., Sugiono, M., Shields, J.D., Peat, D., Gillatt, D. & Harper, S.J. (2002). VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma. Cancer Res. 62, 4123–31.
Berisha, B., Schams, D., Kosmann, M., Amselgruber, W. & 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. Biol. Reprod. 63, 1106–14.
Bruno, J.B., Celestino, J.J.H., Lima-Verde, I.B., Lima, L.F., Matos, M.H.T., Araújo, V.R., Saraiva, M.V.A., Martins, F.S., Name, K.P.O., Campello, C.C., Báo, S.N., Silva, J.R.V. & Figueiredo, J.R. (2009). Expression of vascular endothelial growth factor (VEGF) receptor in goat ovaries and improvement of in vitro caprine preantral follicle survival and growth with VEGF. Reprod. Fertil. Dev. 21, 679–87.
Byrne, A.M., Bouchier-Hayes, D.J. & Harmey, J.H. (2005). Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF). J. Cell. Mol. Med. 9, 777–94.
Cantley, L.C. (2002). The phosphoinositide 3-kinase pathway. Science 296, 1655–7.
Celik-Ozenci, C., Akkoyunhlu, G., Kayisli, U.A., Arici, A. & Demir, R. (2003). Localization of vascular endothelial growth factor in the zona pellucida of developing ovarian follicles in the rat: a possible role in destiny of follicles. Histochem. Cell. Biol. 120, 383–90.
Danforth, D.R., Arbogast, L.K., Ghosh, S., Dickerman, A., Rofagha, R. & Friedman, C.I. (2003). Vascular endothelial growth factor stimulates preantral follicle growth in the rat ovary. Biol. Reprod. 68, 1736–41.
De Vries, C., Escobedo, J.A., Ueno, H., Houck, K., Ferrara, N. & Williams, L.T. (1992). The fms-like tyrosine, kinase, a receptor for vascular endothelial growth factor. Science 255, 989–91.
Dvorak, H.F. (2000). VPF/VEGF and the angiogenic response. Semin. Perinatol. 24, 7578.
Dvorak, H.F., Brown, L.F., Detmar, M. & Dvorak, A.M. (1995). Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am. J. Pathol. 146, 1029–39.
Einspanier, R., Schönfelder, M., Müller, K., Stojkovic, M., Kosmann, M., Wolf, E. & Schams, D. (2002). Expression of the vascular endothelial growth factor and its receptors and effects of VEGF during in vitro maturation of bovine cumulus–oocyte complexes (COC). Mol. Reprod. Dev. 62, 2936.
Ferrara, N. & Alitalo, K. (1999). Clinical applications of angiogenic growth factors and their inhibitors. Nat. Med. 5, 1359–64.
Ferrara, N. & Davis-Smyth, T. (1997). The biology of vascular endothelial growth factor. Endocr. Rev. 18, 425.
Ferrara, N. & Henzel, W.J. (1989). Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem. Biophys. Res. Commun. 161, 851–8.
Ferrari, B., Pezzuto, A., Barusi, L. & Coppola, F. (2006). Follicular fluid vascular endothelial growth factor concentrations are increased during GnRH antagonist/FSH ovarian stimulation cycles. Eur. J. Obstet. Gyn. Reprod. Biol. 124, 70–6.
First, N.L. & Barnes, F.L. (1989). Development of preimplantation mammalian embryos. Prog. Clin. Biol. Res. 294, 151–70.
Fisher, T.E., Zelinski, M.B., Molskness, T.A. & Stouffer, R.L. (2009). Primate preantral follicles produce vascular endothelial growth factor (VEGF) during three-dimensional (3D) culture as a function of growth rate. Fertil. Steril. 92, S64.
Gaulden, M.E. (1992). Maternal age effect: the enigma of Down syndrome and other trisomic conditions. Mutat. Res. 296, 6988.
Gerber, H.P., Dixit, V. & Ferrara, N. (1998a). Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J. Biol. Chem. 273, 13313–6.
Gerber, H.P., McMurtrey, A., Kowalski, J., Yan, M., Keyt, B.A., Dixit, V. & Ferrara, N. (1998b). VEGF regulates endothelial cell survival by the PI3-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J. Biol. Chem. 273, 30336–43.
Gitay-Goren, H., Sofer, S., Vlodavsky, I. & Neufeld, G. (1992). The binding of vascular endothelial growth factor to its receptor is dependent on cell-surface associated heparin-like molecules. J. Biol. Chem. 267, 6093–8.
Gordon, J.D., Messiano, S., Zaloudek, C.J. & Jaffe, R.B. (1996). Vascular endothelial growth factor localization in human ovary and fallopian tubes: possible role in reproductive function and ovarian cyst formation. J. Clin. Endocrinol. Metabol. 81, 353–9.
Greenaway, J., Centry, P.A., Feige, J-J., Lamarre, J. & Petrik, J.J. (2005). Thrombospondin and vascular endothelial growth factor are cyclically expressed in an inverse pattern during bovine ovarian follicle development. Biol. Reprod. 72, 1071–8.
Harata, T., Ando, H., Iwase, A., Nagasaka, T., Mizutani, S. & Kikkawa, F. (2006). Localization of angiotensin II, the AT1 receptor, angiotensin-converting enzyme, aminopeptidase A, adipocyte-derived leucine aminopeptidase, and vascular endothelial growth factor in the human ovary throughout the menstrual cycle. Fertil. Steril. 86, 433–9.
Ho, Q.T. & Kuo, C.J. (2007). Vascular endothelial growth factor: Biology and therapeutic applications. Int. J. Biochem. Cell. Biol. 39, 1349–57.
Holmes, D.I.R. & Zachary, I. (2005). The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease. Gen. Biol. 6, 209.
Houck, K.A., Ferrara, N., Winer, J., Cachianes, G., Li, B. & Leung, D.W. (1991). The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol. Endocrinol. 5, 1806–14.
Iijima, K., Jiang, J-Y., Shimizu, T., Sasada, H. & Sato, E. (2005). Acceleration of follicular development by administration of vascular endothelial growth factor in cycling female rats. J. Reprod. Dev. 51, 161–8.
Jakeman, L.B., Armanini, M., Phillips, H.S. & Ferrara, N. (1993). Developmental expression of binding sites and messenger ribonucleic acid for vascular endothelial growth factor suggests a role for this protein in vasculogenesis and angiogenesis. Endocrinology 133, 848–59.
Jiang, J.Y., Macchiarelli, G., Tsang, B.K. & Sato, E. (2003). Capillary angiogenesis and degeneration in bovine ovarian antral follicles. Reproduction 125, 211–23.
Kaczmarek, M.M., Schams, D. & Ziecik, A.J. (2005). Role of vascular endothelial growth factor in ovarian physiology – an overview. Reprod. Biol. 5, 111–36.
Kaczmarek, M.M., Kowalczyk, A.E., Waclawik, A., Schams, D. & Ziecik, A.J. (2007). expression of vascular endothelial growth factor and its receptors in the porcine corpus luteum during the estrous cycle and early pregnancy. Mol. Reprod. Dev. 74, 730–9.
Kaipainen, A., Korhonen, J., Mustonen, T., Van Hinsbergh, V.W., Fang, G.H., Dumont, D., Breitman, M. & Alitalo, K. (1995). Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc. Natl. Acad. Sci. USA 92, 3566–70.
Karkkainen, M.J., Makinen, T. & Alitalo, K. (2002). Lymphatic endothelium: a new frontier of metastasis research. Nat. Cell Biol. 4, E25.
Kawano, Y., Hasan, K.Z., Fukuda, J., Mine, S. & Miyakawa, I. (2003). Production of vascular endothelial growth factor and angiogenic factor in human follicular fluid. Mol. Cell. Endocrinol. 202, 1923.
Keyt, B.A., Berleau, L.T., Nguyen, H.V., Chen, H., Heinsohn, H., Vandlen, R. & Ferrara, N. (1996). The carboxyl-terminal domain of vascular endothelial growth factor is critical for its mitogenic potency. J. Biol. Chem. 271, 7788–95.
Kezele, P.R., Ague, J.M., Nilsson, E. & Skinner, M.K. (2005). Alterations in the ovarian transcriptome during primordial follicle assembly and development. Biol. Reprod. 72, 241–55.
Koos, R.D. (1995). Increased expression of vascular endothelial growth/permeability factor in the rat ovary following an ovulatory gonadotropin stimulus: potential roles in follicle rupture. Biol. Reprod. 52, 1426–35.
Krussel, J.S., Berh, B., Milki, A.A., Hirchehain, J., Wen, Y., Bielfeld, P. & Polan, M.L. (2001). Vascular endothelial growth factor (VEGF) mRNA splice variants are differentially expressed in human blastocyst. Mol. Hum. Reprod. 7, 5763.
Leung, D.W., Cachianes, G., Kuang, W.J., Goeddel, D.V. & Ferrara, N. (1989). Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246, 1306–9.
Luo, H., Kimura, K., Aoki, M. & Hirako, M. (2002). Effect of vascular endothelial growth factor on maturation, fertilization and developmental competence of bovine oocytes. J. Vet. Med. Sci. 64, 803–6.
Mattioli, M., Barboni, B., Turriani, M., Galeati, G., Zannoni, A., Castellani, G., Berardinelli, P. & Scapolo, P.A. (2001). Follicle activation involves vascular endothelial growth factor production and increased blood vessel extension. Biol. Reprod. 65, 1014–19.
Mignatti, P., Tsuboi, R., Robbins, E. & Rifkin, D.B. (1989). In vitro angiogenesis on the human amniotic membrane: requirement for basic fibroblast growth factor-induced proteinases. J. Cell Biol. 108, 671–82.
Muller, Y.A., Li, B., Christinger, H.W., Wells, J.A., Cunningham, B.C. & de Vos, A.M. (1997). Vascular endothelial growth factor: crystal structure and functional mapping of the kinase domain receptor binding site. Proc. Natl. Acad. Sci. USA 94, 7192–7.
Neufeld, G., Cohen, T., Gengrinovitch, S. & Poltorak, Z. (1999). Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 13, 922.
Otani, N., Minami, S., Yamoto, M., Shikone, T., Otani, H., Nishiyama, R., Otani, T. & Nakano, R. (1999). The vascular endothelial growth factor/fms-like tyrosine kinase system in human ovary during the menstrual cycle and early pregnancy. J. Clin. Endocrinol. Metab. 84, 3845–51.
Papa, P.C., Moura, C.E., Artoni, L.P., Fátima, L.A., Campos, D.B., Marques, J.E. Jr, Baruselli, P.S., Binelli, M., Pfarrer, C. & Leiser, R. (2007). VEGF-system expression in different stages of estrous cycle in superovulated and non-treated water buffalo. Domest. Anim. Endocrinol. 33, 379–89.
Park, J.E., Keller, G-A. & Ferrara, N. (1993). The vascular endothelial growth factor isoforms (VEGF): differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF Mol. Biol. Cell. 4, 1317–26.
Pepper, M.S., Ferrara, N., Orci, L. & Montesano, R. (1992). Potent synergism between basic fibroblast growth factor and vascular endothelial growth factor in the induction of angiogenesis in vitro. Biochem. Biophys. Res. Commun. 189, 824–31.
Pepper, M.S., Vassallim, J-D., Wilks, J.W., Schweigerer, L., Orci, L. & Montesano, R. (1994). Modulation of bovine microvascular endothelial cell proteolytic properties by inhibitors of angiogenesis. J. Cell. Biochem. 55, 419–34.
Quintana, R., Kopcow, L., Sueldo, C., Marconi, G., Rueda, N.G. & Barañao, R.I. (2004). Direct injection of vascular endothelial growth factor into the ovary of mice promotes follicular development. Fertil. Steril. 82, 1101–4.
Rathjen, P.D., Toth, S., Willis, A., Heath, J.K. & Smith, A.G. (1990). Differentiation inhibiting activity is produced in matrix-associated and diffusible forms that are generated by alternate promoter usage. Cell 62, 1105–14.
Redmer, D.A. & Reynolds, L.P. (1996). Angiogenesis in the ovary. Rev. Reprod. 1, 182–92.
Redmer, D.A., Dai, Y., Li, J., Charnock-Jones, D.S., Smith, S.K., Reynolds, L.P. & Moor, R.M. (1996). Characterization and expression of vascular endothelial growth factor (VEGF) in the ovine corpus luteum. J. Reprod. Fertil. 108, 157–65.
Roberts, W.G. & Palade, G.E. (1995). Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J. Cell Sci. 108, 2369–79.
Roberts, A.E., Arbogast, L.K., Friedman, C.I., Cohn, D.E., Kaumaya, P.T. & Danforth, D.R. (2007). Neutralization of endogenous vascular endothelial growth factor depletes primordial follicles in the mouse ovary. Biol. Reprod. 76, 218–23.
Sasisekharan, R., Moses, M.A., Nugent, M.A., Cooney, C.L. & Langer, R. (1994). Heparinase inhibits neovascularization. Proc. Natl. Acad. Sci. USA 91, 1524–8.
Senger, D.R., Galli, S.J., Dvorak, A.M., Perruzzi, C.A., Harvey, V.S. & Dvorak, H.F. (1983). Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219, 983–5.
Sharma, R.K. & Sudan, N. (2010). Immunohistochemical mapping of vascular endothelial growth factor during follicular growth in goat ovary. J. Cell Tis. Res. 10, 2101–4.
Shibuya, M., Yamaguchi, S., Yamane, A., Ikeda, T., Tojo, A., Matsushime, H. & Sato, M. (1990). Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (Flt) closely related to the fms family. Oncogene 5, 519–24.
Shifren, J.A., Tseng, J.F., Zaloudek, C.J., Ryan, Y.P., Meng, Y.G., Ferrara, N., Jaffe, R.B. & Taylor, R.N. (1996). Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis. J. Clin. Endocrinol. Metabol. 81, 3112–8.
Shimizu, T., Jiang, J.Y., Sasada, H. & Sato, E. (2002). Changes of mRNA expression of angiogenic factors and related receptors during follicular development in gilts. Biol. Reprod. 67, 1846–52.
Shimizu, T., Kawahara, M., Abe, Y., Yokoo, M., Sasada, H. & Sato, E. (2003). Follicular microvasculature and angiogenic factors in the ovaries of domestic animals J. Reprod. Dev. 49, 181–92.
Shin, S.Y., Lee, J.Y., Lee, E.Y., Choi, J.Y., Yoon, B.K., Bae, D. & Choi, D. (2006). Protective effect of vascular endothelial growth factor (VEGF) in frozen–thawed granulosa cells is mediated by inhibition of apoptosis. Eur. J. Obstet. Gyn. Reprod. Biol. 125, 233–38.
Shweiki, D., Itin, A., Neufeld, G., Gitay-Goren, H. & Keshed, E. (1993). Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J. Clin. Invest. 91, 2235–43.
Stouffer, R.L., Martínez-Chequer, J.C., Molskness, T.A., Xu, F. & Hazzard, T.M. (2001). Regulation and action of angiogenic factors in the primate ovary. Arch. Med. Res. 32, 567–75.
Suzuki, T., Sasano, H., Takaya, R., Fukaya, T., Yajima, A. & Nagura, H. (1998). Cyclic changes of vasculature and vascular phenotypes in normal human ovaries. Hum. Reprod. 13, 953–9.
Tamanini, C. & De Ambrogi, M. (2004). Angiogenesis in developing follicle and corpus luteum. Reprod. Dom. Ani. 39, 206–16.
Taylor, P.D., Hillier, S.G. & Fraser, H.M. (2004). Effects of GnRH antagonist treatment on follicular development and angiogenesis in the primate ovary. J. Endocrinol. 183, 117.
Terman, B.I., Dougher-Vermazen, M., Carrion, M.E., Dimitrov, D., Armellino, D.C., Gospodarowicz, D. & Bohlen, P. (1992). Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem. Biophys. Res. Commun. 187, 1579–86.
Tischer, E., Gospodarowicz, D., Mitchell, R., Silva, M., Schilling, J., Lau, K., Crisp, T., Fiddes, J.C. & Abraham, J.A. (1989). Vascular endothelial growth factor: a new member of the platelet-derived growth factor gene family. Biochem. Biophys. Res. Commun. 165, 1198–206.
Tischer, E., Mitchell, R., Hartmann, T., Silva, M., Gospodarowicz, D., Fiddes, J. & Abraham, J. (1991). The human gene for vascular endothelial growth factor. J. Biol. Chem. 266, 11947–54.
Trounson, A.O., Willadsen, S.M. & Rowson, L.E.A. (1977). Fertilization and development capability of bovine follicular oocytes matured in vitro and in vivo and transferred to the oviducts of rabbits and cows. J. Reprod. Fertil. 51, 321–7.
Van Blerkom, J., Antczak, M. & Schrader, R. (1997). The developmental potential of the human oocyte is related to the dissolved oxygen content of follicular fluid: association with vascular endothelial growth factor levels and perifollicular blood flow characteristics. Hum. Reprod. 12, 1047–55.
Van den Hurk, R. & Zhao, J. (2005). Formation of mammalian oocytes and their growth differentiation and maturation within ovarian follicles. Theriogenology 63, 1717–51.
Wulff, C., Wiegand, S.J., Saunders, P.T.K., Scobie, G.A. & Fraser, H.M. (2001). Angiogenesis during follicular development in the primate and its inhibition by treatment with truncated Flt-1-Fc (vascular endothelial growth factor trapA40). Endocrinology 142, 3244–54.
Yang, M.Y. & Fortune, J.E. (2007). Vascular endothelial growth factor stimulates the primary to secundary follicle transition in bovine follicles in vitro. Mol. Reprod. Dev. 74, 1095–104.
Yang, H., Lee, H.H., Lee, H.C., Ko, D.S. & Kim, S.S. (2008). Assessment of vascular endothelial growth factor expression and apoptosis in the ovarian graft: can exogenous gonadotropin promote angiogenesis after ovarian transplantation? Fertil. Steril. 90, 1550–8.
Yuan, F., Chen, Y., Dellian, M., Safabakhsh, N., Ferrara, N. & Jain, R.K. (1996). Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody. Proc. Natl. Acad. Sci. USA 93, 14765–70.
Zimmermann, R.C., Xiao, E., Husami, N., Sauer, M.V., Lobo, R., Kitajewski, J. & Ferin, M. (2001). Short-term administration of antivascular endothelial growth factor antibody in the late follicular phase delays follicular development in the rhesus monkey. J. Clin. Endocrinol. Metab. 86, 768–72.
Zimmermann, R.C., Hartman, T., Kavic, S., Pauli, S.A., Bohlen, P., Sauer, M.V. & Kitajewski, J. (2003). Vascular endothelial growth factor receptor 2–mediated angiogenesis is essential for gonadotropin-dependent follicle development. J. Clin. Invest. 112, 659–69.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Zygote
  • ISSN: 0967-1994
  • EISSN: 1469-8730
  • URL: /core/journals/zygote
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed