Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Presence of vascular endothelial growth factor during the first half of IVM improves the meiotic and developmental competence of porcine oocytes from small follicles

Tra M. T. Bui A , Khánh X. Nguyễn A , Asako Karata A , Pilar Ferré A , Minh T. Trần A , Takuya Wakai A and Hiroaki Funahashi A B

A Department of Animal Science, Graduate School of Environmental and Life Sciences, Okayama University, Tsushima-Naka, Kita-Ku, Okayama 700-8530, Japan.

B Corresponding author. Email: hirofun@okayama-u.ac.jp

Reproduction, Fertility and Development - https://doi.org/10.1071/RD16321
Submitted: 1 May 2016  Accepted: 20 October 2016   Published online: 12 December 2016

Abstract

The aim of the present study was to investigate the effect of vascular endothelial growth factor (VEGF) on the meiotic and developmental competence of porcine oocytes from small follicles (SF; 0.5–3 mm diameter). When cumulus–oocyte complexes (COCs) from medium-sized follicles (MF; 3–6 mm diameter) and SF were cultured for IVM, the maturation rates were significantly higher for oocytes from MF than SF. Concentrations of VEGF in the medium were significantly higher for COCs cultured from MF than SF. When COCs from SF were exposed to 200 ng mL–1 VEGF during the first 20 h of IVM, the maturation rate improved significantly and was similar to that of oocytes derived from MF. The fertilisability of oocytes was also significantly higher than that of VEGF-free SF controls. Following parthenogenetic activation, the blastocyst formation rate improved significantly when SF COC culture was supplemented with 200 ng mL–1 VEGF, with the rate similar to that of oocytes from MF. The results of the present study indicate that VEGF markedly improves the meiotic and developmental competence of oocytes derived from SF, especially at a concentration of 200 ng mL–1 during the first 20 h of IVM.

Additional keyword: pig.


References

Abir, R., Ao, A., Zhang, X. Y., Garor, R., Nitke, S., and Fisch, B. (2010). Vascular endothelial growth factor A and its two receptors in human preantral follicles from fetuses, girls, and women. Fertil. Steril. 93, 2337–2347.
Vascular endothelial growth factor A and its two receptors in human preantral follicles from fetuses, girls, and women.CrossRef | 1:CAS:528:DC%2BC3cXms1ylsb0%3D&md5=79dbec1968c5784ce5954a93af63a267CAS | open url image1

Akaki, Y., Yoshioka, K., Noguchi, M., Hoshi, H., and Funahashi, H. (2009). Successful piglet production in a chemically defined system for in-vitro production of porcine embryos: dibutyryl cyclic AMP and epidermal growth factor-family peptides support in-vitro maturation of oocytes in the absence of gonadotropins. J. Reprod. Dev. 55, 446–453.
Successful piglet production in a chemically defined system for in-vitro production of porcine embryos: dibutyryl cyclic AMP and epidermal growth factor-family peptides support in-vitro maturation of oocytes in the absence of gonadotropins.CrossRef | 1:CAS:528:DC%2BD1MXhsFOmtLfM&md5=b808962f8d1da1f92cbb021b829097feCAS | open url image1

Anchordoquy, J. M., Anchordoquy, J. P., Testa, J. A., Sirini, M. A., and Furnus, C. C. (2015). Influence of vascular endothelial growth factor and cysteamine on in vitro bovine oocyte maturation and subsequent embryo development. Cell Biol. Int. 39, 1090–1098.
Influence of vascular endothelial growth factor and cysteamine on in vitro bovine oocyte maturation and subsequent embryo development.CrossRef | 1:CAS:528:DC%2BC2MXhsFejtbzE&md5=d89ccd294eaae5c86c1fa4e78f92da00CAS | open url image1

Barboni, B., Turriani, M., Galeati, G., Spinaci, M., Bacci, M. L., Forni, M., and Mattioli, M. (2000). Vascular endothelial growth factor production in growing pig antral follicles. Biol. Reprod. 63, 858–864.
Vascular endothelial growth factor production in growing pig antral follicles.CrossRef | 1:CAS:528:DC%2BD3cXmtFCiu7c%3D&md5=6d9d9887b3c4e2eb19372af34ef72725CAS | open url image1

Berisha, B., Schams, D., Kosmann, M., Amselgruber, W., and Einspanier, R. (2000). Expression and localisation of vascular endothelial growth factor and basic fibroblast growth factor during the final growth of bovine ovarian follicles. J. Endocrinol. 167, 371–382.
Expression and localisation of vascular endothelial growth factor and basic fibroblast growth factor during the final growth of bovine ovarian follicles.CrossRef | 1:CAS:528:DC%2BD3MXjtVCqtg%3D%3D&md5=05cd5d5c9eb2eb5dc270dd08f503f183CAS | open url image1

Biswas, D., and Hyun, S. H. (2011). Supplementation with vascular endothelial growth factor during in vitro maturation of porcine cumulus oocyte complexes and subsequent developmental competence after in vitro fertilization. Theriogenology 76, 153–160.
Supplementation with vascular endothelial growth factor during in vitro maturation of porcine cumulus oocyte complexes and subsequent developmental competence after in vitro fertilization.CrossRef | 1:CAS:528:DC%2BC3MXntFKitbk%3D&md5=871fd7f3fb1c56251e745bd68a626216CAS | open url image1

Biswas, D., Jeon, Y.-B., Kim, G. H., Jeung, E. B., and Hyun, S. H. (2010). Effect of vascular endothelial growth factor on in vitro porcine oocyte maturation and subsequent developmental competence after parthenogenesis. J. Anim. Vet. Advances 9, 2924–2931.
Effect of vascular endothelial growth factor on in vitro porcine oocyte maturation and subsequent developmental competence after parthenogenesis.CrossRef | 1:CAS:528:DC%2BC38XktV2jsr4%3D&md5=6d089076fa84835c62819b2d79f6441dCAS | open url image1

Biswas, D., Jung, E. M., Jeung, E. B., and Hyun, S. H. (2011). Effects of vascular endothelial growth factor on porcine preimplantation embryos produced by in vitro fertilization and somatic cell nuclear transfer. Theriogenology 75, 256–267.
Effects of vascular endothelial growth factor on porcine preimplantation embryos produced by in vitro fertilization and somatic cell nuclear transfer.CrossRef | 1:CAS:528:DC%2BC3cXhsF2isbnP&md5=4d683abb403019f5b13f2743ff226b5fCAS | open url image1

Bruno, J. B., Matos, M. H. T., Chaves, R. N., Celestino, J. J. H., Saraiva, M. V. A., Lima-Verde, I. B., Araújo, V. R., and Figueiredo, J. R. (2009). Angiogenic factors and ovarian follicle development. Anim. Reprod. 6, 371–379. open url image1

Cognie, Y., Benoit, F., Poulin, N., Khatir, H., and Driancourt, M. A. (1998). Effect of follicle size and of the FecB Booroola gene on oocyte function in sheep. J. Reprod. Fertil. 112, 379–386.
Effect of follicle size and of the FecB Booroola gene on oocyte function in sheep.CrossRef | 1:CAS:528:DyaK1cXktVent7g%3D&md5=52b13d4342d4dbfe037d2193e01422c7CAS | open url image1

Cooper, D. K., Hara, H., Ezzelarab, M., Bottino, R., Trucco, M., Phelps, C., Ayares, D., and Dai, Y. (2013). The potential of genetically-engineered pigs in providing an alternative source of organs and cells for transplantation. J. Biomed. Res. 27, 249–253.
The potential of genetically-engineered pigs in providing an alternative source of organs and cells for transplantation.CrossRef | open url image1

Crozet, N., Ahmed-Ali, M., and Dubos, M. P. (1995). Developmental competence of goat oocytes from follicles of different size categories following maturation, fertilization and culture in vitro. J. Reprod. Fertil. 103, 293–298.
Developmental competence of goat oocytes from follicles of different size categories following maturation, fertilization and culture in vitro.CrossRef | 1:CAS:528:DyaK2MXlvV2rtLg%3D&md5=fcede29c9c05e26ec7bd368cfce928e1CAS | open url image1

Einspanier, R., Schonfelder, M., Muller, K., Stojkovic, M., Kosmann, M., Wolf, E., and 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, 29–36.
Expression of the vascular endothelial growth factor and its receptors and effects of VEGF during in vitro maturation of bovine cumulus–oocyte complexes (COC).CrossRef | 1:CAS:528:DC%2BD38XivVChurs%3D&md5=924694ed77c93d3cb45a5237804f71c0CAS | open url image1

Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O’Shea, K. S., Powell-Braxton, L., Hillan, K. J., and Moore, M. W. (1996). Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380, 439–442.
Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene.CrossRef | 1:CAS:528:DyaK28XitVKqtLk%3D&md5=3aaf516274494e531d9f29505187f34bCAS | open url image1

Ferrara, N., Gerber, H. P., and LeCouter, J. (2003). The biology of VEGF and its receptors. Nat. Med. 9, 669–676.
The biology of VEGF and its receptors.CrossRef | 1:CAS:528:DC%2BD3sXktFOnur4%3D&md5=f9a619eb1e8c5ea6d315e9e9b457d532CAS | open url image1

Funahashi, H. (2003). Polyspermic penetration in porcine IVM–IVF systems. Reprod. Fertil. Dev. 15, 167–177.
Polyspermic penetration in porcine IVM–IVF systems.CrossRef | open url image1

Funahashi, H. (2005). Effect of beta-mercaptoethanol during in vitro fertilization procedures on sperm penetration into porcine oocytes and the early development in vitro. Reproduction 130, 889–898.
Effect of beta-mercaptoethanol during in vitro fertilization procedures on sperm penetration into porcine oocytes and the early development in vitro.CrossRef | 1:CAS:528:DC%2BD28Xkt12nuw%3D%3D&md5=e6611e35e0a6f028da0f47f2880f941bCAS | open url image1

Funahashi, H., and Day, B. N. (1993). Effects of follicular fluid at fertilization in vitro on sperm penetration in pig oocytes. J. Reprod. Fertil. 99, 97–103.
Effects of follicular fluid at fertilization in vitro on sperm penetration in pig oocytes.CrossRef | 1:STN:280:DyaK2c7htFWhsA%3D%3D&md5=3e8a283bd77ff1ff86ac18ff3d009c64CAS | open url image1

Funahashi, H., Cantley, T. C., and Day, B. N. (1997). Synchronization of meiosis in porcine oocytes by exposure to dibutyryl cyclic adenosine monophosphate improves developmental competence following in vitro fertilization. Biol. Reprod. 57, 49–53.
Synchronization of meiosis in porcine oocytes by exposure to dibutyryl cyclic adenosine monophosphate improves developmental competence following in vitro fertilization.CrossRef | 1:CAS:528:DyaK2sXktFCntb0%3D&md5=aea86b0b127c2eb62a489e021db24d1eCAS | open url image1

Galli, C., Lagutina, I., and Lazzari, G. (2003). Introduction to cloning by nuclear transplantation. Cloning Stem Cells 5, 223–232.
Introduction to cloning by nuclear transplantation.CrossRef | 1:CAS:528:DC%2BD2cXislaqtg%3D%3D&md5=4f55121f98ca9f842a187200c1917addCAS | open url image1

Gosden, R. G., and Telfer, E. (1987). Number of follicles and oocytes in mammalian ovaries and their allometric relationships. J. Zool. (Lond.) 211, 169–175.
Number of follicles and oocytes in mammalian ovaries and their allometric relationships.CrossRef | open url image1

Greenaway, J., Connor, K., Pedersen, H. G., Coomber, B. L., LaMarre, J., and Petrik, J. (2004). Vascular endothelial growth factor and its receptor, Flk-1/KDR, are cytoprotective in the extravascular compartment of the ovarian follicle. Endocrinology 145, 2896–2905.
Vascular endothelial growth factor and its receptor, Flk-1/KDR, are cytoprotective in the extravascular compartment of the ovarian follicle.CrossRef | 1:CAS:528:DC%2BD2cXkt12gu7w%3D&md5=fa741a53f34d4a5605871839e6101669CAS | open url image1

Hanahan, D. (1997). Signaling vascular morphogenesis and maintenance. Science 277, 48–50.
Signaling vascular morphogenesis and maintenance.CrossRef | 1:CAS:528:DyaK2sXksVyhtrk%3D&md5=35fa78b50a13e3fe69f3f852e2df85b2CAS | open url image1

Kere, M., Siriboon, C., Liao, J. W., Lo, N. W., Chiang, H. I., Fan, Y. K., Kastelic, J. P., and Ju, J. C. (2014). Vascular endothelial growth factor A improves quality of matured porcine oocytes and developing parthenotes. Domest. Anim. Endocrinol. 49, 60–69.
Vascular endothelial growth factor A improves quality of matured porcine oocytes and developing parthenotes.CrossRef | 1:CAS:528:DC%2BC2cXhtlGgtrnJ&md5=8606bbbc44ca8fddc9c34cd723472171CAS | open url image1

Khatir, H., Anouassi, A., and Tibary, A. (2007). Effect of follicular size on in vitro developmental competence of oocytes and viability of embryos after transfer in the dromedary (Camelus dromedarius). Anim. Reprod. Sci. 99, 413–420.
Effect of follicular size on in vitro developmental competence of oocytes and viability of embryos after transfer in the dromedary (Camelus dromedarius).CrossRef | 1:STN:280:DC%2BD2s7pvVOrtg%3D%3D&md5=1fe8a41a54a64770d5363b4ebc5df855CAS | open url image1

Kohata, C., Izquierdo-Rico, M. J., Romar, R., and Funahashi, H. (2013). Development competence and relative transcript abundance of oocytes derived from small and medium follicles of prepubertal gilts. Theriogenology 80, 970–978.
Development competence and relative transcript abundance of oocytes derived from small and medium follicles of prepubertal gilts.CrossRef | open url image1

Kosaka, N., Sudo, N., Miyamoto, A., and Shimizu, T. (2007). Vascular endothelial growth factor (VEGF) suppresses ovarian granulosa cell apoptosis in vitro. Biochem. Biophys. Res. Commun. 363, 733–737.
Vascular endothelial growth factor (VEGF) suppresses ovarian granulosa cell apoptosis in vitro.CrossRef | 1:CAS:528:DC%2BD2sXhtFCjtrrK&md5=c9dea87fde35010819899021acbd0792CAS | open url image1

Leung, D. W., Cachianes, G., Kuang, W. J., Goeddel, D. V., and Ferrara, N. (1989). Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246, 1306–1309.
Vascular endothelial growth factor is a secreted angiogenic mitogen.CrossRef | 1:CAS:528:DyaK3cXls1GltLo%3D&md5=f23e44e86532f81fd7c5e89dfee43ca5CAS | open url image1

Lonergan, P., Monaghan, P., Rizos, D., Boland, M. P., and Gordon, I. (1994). Effect of follicle size on bovine oocyte quality and developmental competence following maturation, fertilization, and culture in vitro. Mol. Reprod. Dev. 37, 48–53.
Effect of follicle size on bovine oocyte quality and developmental competence following maturation, fertilization, and culture in vitro.CrossRef | 1:STN:280:DyaK2c7ns1Wltw%3D%3D&md5=721dc5e11da3fe900d48a8938b833bb2CAS | open url image1

Luo, H., Kimura, K., Aoki, M., and Hirako, M. (2002). Effect of vascular endothelial growth factor on maturation, fertilization and developmental competence of bovine oocytes. J. Vet. Med. Sci. 64, 803–806.
Effect of vascular endothelial growth factor on maturation, fertilization and developmental competence of bovine oocytes.CrossRef | 1:CAS:528:DC%2BD38XosFSrsr0%3D&md5=b3ba2fe4e38b20ffef81389cccb8320dCAS | open url image1

Marchal, R., Vigneron, C., Perreau, C., Bali-Papp, A., and Mermillod, P. (2002). Effect of follicular size on meiotic and developmental competence of porcine oocytes. Theriogenology 57, 1523–1532.
Effect of follicular size on meiotic and developmental competence of porcine oocytes.CrossRef | 1:STN:280:DC%2BD38zhtFykug%3D%3D&md5=00c2baf29980e151c73493ee2b789a22CAS | open url image1

Mattioli, M., Barboni, B., Turriani, M., Galeati, G., Zannoni, A., Castellani, G., Berardinelli, P., and Scapolo, P. A. (2001). Follicle activation involves vascular endothelial growth factor production and increased blood vessel extension. Biol. Reprod. 65, 1014–1019.
Follicle activation involves vascular endothelial growth factor production and increased blood vessel extension.CrossRef | 1:CAS:528:DC%2BD3MXnt1Cmsr4%3D&md5=51ad51fd3fabd6494f33304a5c8b86e5CAS | open url image1

Otoi, T., Fujii, M., Tanaka, M., Ooka, A., and Suzuki, T. (2000). Oocyte diameter in relation to meiotic competence and sperm penetration. Theriogenology 54, 535–542.
Oocyte diameter in relation to meiotic competence and sperm penetration.CrossRef | 1:STN:280:DC%2BD3crht1KhtA%3D%3D&md5=c6153e90fa3179577bb3505c3dda73aaCAS | open url image1

Raghu, H. M., Nandi, S., and Reddy, S. M. (2002). Follicle size and oocyte diameter in relation to developmental competence of buffalo oocytes in vitro. Reprod. Fertil. Dev. 14, 55–61.
Follicle size and oocyte diameter in relation to developmental competence of buffalo oocytes in vitro.CrossRef | 1:STN:280:DC%2BD38zgvFemsg%3D%3D&md5=05ef5ce2cf86de865fe4cb37d658b79bCAS | open url image1

Romaguera, R., Casanovas, A., Morato, R., Izquierdo, D., Catala, M., Jimenez-Macedo, A. R., Mogas, T., and Paramio, M. T. (2010a). Effect of follicle diameter on oocyte apoptosis, embryo development and chromosomal ploidy in prepubertal goats. Theriogenology 74, 364–373.
Effect of follicle diameter on oocyte apoptosis, embryo development and chromosomal ploidy in prepubertal goats.CrossRef | 1:STN:280:DC%2BC3cnntVGltA%3D%3D&md5=96f4106cd716e2072c6651b5ab2edd10CAS | open url image1

Romaguera, R., Morato, R., Jimenez-Macedo, A. R., Catala, M., Roura, M., Paramio, M. T., Palomo, M. J., Mogas, T., and Izquierdo, D. (2010b). Oocyte secreted factors improve embryo developmental competence of COCs from small follicles in prepubertal goats. Theriogenology 74, 1050–1059.
Oocyte secreted factors improve embryo developmental competence of COCs from small follicles in prepubertal goats.CrossRef | 1:STN:280:DC%2BC3cjpvFyisg%3D%3D&md5=a41dda4dff8e8257366aa4d6257d95f6CAS | open url image1

Romar, R., Funahashi, H., and Coy, P. (2016). In vitro fertilization in pigs: new molecules and protocols to consider in the forthcoming years. Theriogenology 85, 125–134.
In vitro fertilization in pigs: new molecules and protocols to consider in the forthcoming years.CrossRef | 1:CAS:528:DC%2BC2MXht12ktbbI&md5=8c2495b4ea2ddabe272e9085f046e058CAS | open url image1

Senger, D. R., Galli, S. J., Dvorak, A. M., Perruzzi, C. A., Harvey, V. S., and Dvorak, H. F. (1983). Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219, 983–985.
Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid.CrossRef | 1:STN:280:DyaL3s7hvF2mtw%3D%3D&md5=15b98c4ec430441d2f9f5acb06ed0d74CAS | open url image1

Shimizu, T., Jiang, J. Y., Iijima, K., Miyabayashi, K., Ogawa, Y., Sasada, H., and Sato, E. (2003). Induction of follicular development by direct single injection of vascular endothelial growth factor gene fragments into the ovary of miniature gilts. Biol. Reprod. 69, 1388–1393.
Induction of follicular development by direct single injection of vascular endothelial growth factor gene fragments into the ovary of miniature gilts.CrossRef | 1:CAS:528:DC%2BD3sXnsV2nsbk%3D&md5=c2589a31081cd407a0f2f067b255dcd8CAS | open url image1

Shin, S. Y., Lee, J. Y., Lee, E., Choi, J., Yoon, B. K., Bae, D., and 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. Gynecol. Reprod. Biol. 125, 233–238.
Protective effect of vascular endothelial growth factor (VEGF) in frozen–thawed granulosa cells is mediated by inhibition of apoptosis.CrossRef | 1:CAS:528:DC%2BD28XjtFGktLg%3D&md5=d4920055fcff6bb74eac91d6f3b5a0c4CAS | open url image1

Wang, W. H., Niwa, K., and Okuda, K. (1991). In-vitro penetration of pig oocytes matured in culture by frozen–thawed ejaculated spermatozoa. J. Reprod. Fertil. 93, 491–496.
In-vitro penetration of pig oocytes matured in culture by frozen–thawed ejaculated spermatozoa.CrossRef | 1:STN:280:DyaK387lslSrsw%3D%3D&md5=edabf4b778886965f7d529ee87a1c60aCAS | open url image1

Wang, B., Gao, Y., Xiao, Z., Chen, B., Han, J., Zhang, J., Wang, X., and Dai, J. (2009). Erk1/2 promotes proliferation and inhibits neuronal differentiation of neural stem cells. Neurosci. Lett. 461, 252–257.
Erk1/2 promotes proliferation and inhibits neuronal differentiation of neural stem cells.CrossRef | 1:CAS:528:DC%2BD1MXosVehu78%3D&md5=0d4d531902dd442cb37a635f7e9a32b1CAS | open url image1

Watson, A. J. (2007). Oocyte cytoplasmic maturation: a key mediator of oocyte and embryo developmental competence. J. Anim. Sci. 85, E1–E3.
Oocyte cytoplasmic maturation: a key mediator of oocyte and embryo developmental competence.CrossRef | 1:STN:280:DC%2BD2s7ntFensw%3D%3D&md5=9754986377fc919eeee199018d9afa02CAS | open url image1

Wittmaack, F. M., Kreger, D. O., Blasco, L., Tureck, R. W., Mastroianni, L., and Lessey, B. A. (1994). Effect of follicular size on oocyte retrieval, fertilization, cleavage, and embryo quality in in vitro fertilization cycles: a 6-year data collection. Fertil. Steril. 62, 1205–1210.
Effect of follicular size on oocyte retrieval, fertilization, cleavage, and embryo quality in in vitro fertilization cycles: a 6-year data collection.CrossRef | 1:STN:280:DyaK2M%2Fks1Cjsw%3D%3D&md5=e9e0138816edd76211bfe1185fcc0c96CAS | open url image1

Yang, M. Y., and Fortune, J. E. (2007). Vascular endothelial growth factor stimulates the primary to secondary follicle transition in bovine follicles in vitro. Mol. Reprod. Dev. 74, 1095–1104.
Vascular endothelial growth factor stimulates the primary to secondary follicle transition in bovine follicles in vitro.CrossRef | 1:CAS:528:DC%2BD2sXpt1alsL8%3D&md5=8c3d99cc9f2b3002aa96a01bae664545CAS | open url image1

Yoon, K. W., Shin, T. Y., Park, J. I., Roh, S., Lim, J. M., Lee, B. C., Hwang, W. S., and Lee, E. S. (2000). Development of porcine oocytes from preovulatory follicles of different sizes after maturation in media supplemented with follicular fluids. Reprod. Fertil. Dev. 12, 133–139.
Development of porcine oocytes from preovulatory follicles of different sizes after maturation in media supplemented with follicular fluids.CrossRef | 1:STN:280:DC%2BD3MvjsFejtw%3D%3D&md5=35214753277d82d7847eb78526020010CAS | open url image1

Yoshioka, K., Suzuki, C., and Onishi, A. (2008). Defined system for in vitro production of porcine embryos using a single basic medium. J. Reprod. Dev. 54, 208–213.
Defined system for in vitro production of porcine embryos using a single basic medium.CrossRef | open url image1

Zimmermann, R. C., Xiao, E., Bohlen, P., and Ferin, M. (2002). Administration of antivascular endothelial growth factor receptor 2 antibody in the early follicular phase delays follicular selection and development in the rhesus monkey. Endocrinology 143, 2496–2502.
Administration of antivascular endothelial growth factor receptor 2 antibody in the early follicular phase delays follicular selection and development in the rhesus monkey.CrossRef | 1:CAS:528:DC%2BD38XltVymsL0%3D&md5=57ca0ce2273a2d38be10c5028af434bfCAS | open url image1



Export Citation