Abstract
Despite the fact that the fundamental principle underlying the most common method of culture media constitution is that of mimicking the natural environment of the preimplantation embryo, one major difference that remains between current embryo culture media and in vivo conditions is the absence of growth factors in vitro. Numerous growth factors are known to be present in the in vivo environment of human and nonhuman preimplantation embryos, often with peak concentrations corresponding to when fertilization and preimplantation embryo growth would occur. Although these growth factors are found in very small concentrations, they have a profound effect on tissue growth and differentiation through attachment to factor-specific receptors on cell surfaces. Receptors for many different growth factors have also been detected in human preimplantation embryos. Preimplantation embryos themselves express many growth factors. The growth factors and receptors are metabolically costly to produce, and thus their presence in the environment of the preimplantation embryo and in the embryo respectively strongly implies that embryos are designed to encounter and respond to the corresponding factors. Studies of embryo coculture also indirectly suggest that growth factors can improve in vitro development. Several animal and human studies attest to a probable beneficial effect of addition of growth factors to culture media. However, there is still ambiguity regarding the exact role of growth factors in embryonic development, the optimal dose of growth factors to be added to culture media, the combinatorial effect and endocrine of growth factors in embryonic development.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Behr B, Wang H (2004) Effect of culture conditions on IVF outcome. Eur J Obstet Gynecol Reprod Biol 115S:S72–S76
Thompson J, Mitchell M, Kind K (2007) Embryo culture and long-term consequences. Reprod Fertil Dev 19(1):43–52
Whittens W, Biggers J (1968) Complete development in vitro of the pre-implantation stages of the mouse in a simple chemically defined medium. J Reprod Fertil 17(2):399–401
Payne S, Munday R, Thompson J (1992) Addition of superoxide dismutase and catalase does not necessarily overcome developmental retardation of one-cell mouse embryos during in-vitro culture. Reprod Fertil Dev 4:167–174
Ho Y, Doherty A, Schultz R (1994) Mouse preimplantation embryo development in vitro, effect of sodium concentration in culture media onRNAsynthesis and accumulation and gene expression. Mol Reprod Dev 38:131–141
Wrenzycki C, Herrman D, Carnwarth J, Niemann H (1999) Alterations in the relative abundance of gene transcripts in preimplantation bovine embryos cultured in medium supplemented with either serum or PVA. Mol Reprod Dev 53:8–18
Wrenzycki C, Herrmann D, Keskintepe L, Martins A Jr, Sirisathien S, Brackett B, Niemann H (2001) Effects of culture system and protein supplementation on mRNA expression in pre-implantation bovine embryos. Hum Reprod 16:893–901
Niemann H, Wrenzycki C (2000) Alterations of expression of developmentally important genes in preimplantation bovine embryos by in vitro culture conditions, implications for subsequent development. Theriogenology 53:21–34
Rizos D, Lonergan P, Boland M, Arroyo-Garcia R, Pintado B, De La Fuente J, Gutierrez-Adan A (2002) Analysis of differential messenger RNA expression between bovine blastocysts produced in different culture systems, implications for blastocyst quality. Biol Reprod 66:589–595
Lonergan P, Rizos D, Gutierrez-Adan A, Fair T, Boland M (2003) Oocyte and embryo quality, effect of origin, culture condition and gene expression patterns. Reprod Domest Anim 38:259–267
Lonergan P, Pedersen H, Rizos D, Greve T, Thomsen P, Fair T, Evans A, Boland M (2004) Effect of the postfertilization culture environment on the incidence of chromosome aberrations in bovine blastocysts. Biol Reprod 71:1096–1100
Kind K, Collett R, Harvey A, Thompson J (2005) Oxygen-regulated expression of GLUT-1, GLUT-3, and VEGF in the mouse blastocyst. Mol Reprod Dev 70:37–44
Bertolini M, Moyer A, Mason J, Batchelder C, Hoffert K et al (2004) Evidence of increased substrate availability to in vitro-derived bovine foetuses and association with accelerated conceptus growth. Reproduction 128:341–354
Sjoblom C, Roberts C, Wikland M, Robertson S (2005) Granulocyte–macrophage colony-stimulating factor alleviates adverse consequences of embryo culture on fetal growth trajectory and placental morphogenesis. Endocrinology 146:2142–2153
Farin P, Farin C (1995) Transfer of bovine embryos produced in vivo or in vitro, survival and fetal development. Biol Reprod 52:676–682
Maxfield E, Sinclair K, Broadbent P et al (1998) Short-term culture of ovine embryos modifies fetal myogenesis. Am J Physiol 274:E1121–E1123
Crosier A, Farin C, Rodriguez K et al (2002) Development of skeletal muscle and expression of candidate genes in bovine fetuses from embryos produced in vivo or in vitro. Biol Reprod 67:401–408
Young L, Fernandes K, McEvoy T et al (2001) Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat Genet 27:153–154
Hiendleder S, Mund C, Reichenbach H et al (2004) Tissue-specific elevated genomic cytosine methylation levels are associated with an overgrowth phenotype of bovine fetuses derived by in vitro techniques. Biol Reprod 71:217–223
Hiendleder S, Wirtz M, Mund C et al (2006) Tissue-specific effects of in vitro fertilization procedures on genomic cytosine methylation levels in overgrown and normal sized bovine fetuses. Biol Reprod 75:17–23
Sangild P, Schmidt M, Jacobsen H et al (2000) Blood chemistry, nutrient metabolism, and organ weights in fetal and newborn calves derived from in vitro-produced bovine embryos. Biol Reprod 62:1495–1504
van Wagtendonk-de Leeuw A, Mullaart E, de Roos A et al (2000) Effects of different reproduction techniques, AI MOET or IVP, on health and welfare of bovine offspring. Theriogenology 53:575–597
McEvoy T, Sinclair K, Broadbent P et al (1998) Postnatal growth and development of Simmental calves derived from in vivo or in vitro embryos. Reprod Fertil Dev 10:459–464
Rivera R, Stein P, Weaver J et al (2008) Manipulations of mouse embryos prior to implantation result in aberrant expression of imprinted genes on day 9.5 of development. Hum Mol Genet 17:1–14
Li T, Vu T, Ulaner G, Littman E, Ling J, Chen H, Hu J, Behr B, Giudice L, Hoffman A (2005) IVF results in de novo DNA methylation and histone methylation at an Igf2-H19 imprinting epigenetic switch. Mol Hum Reprod 11(9):631–640
Fauque P, Jouannet P, Lesaffre C et al (2007) Assisted reproductive technology affects developmental kinetics, H19 imprinting control region methylation and H19 gene expression in individual mouse embryos. BMC Dev Biol 7:116
Richter K (2008) The importance of growth factors for preimplantation embryo development and in-vitro culture. Curr Obstet Gynecol 20(3):292–304
Lidegaard O, Pinborg A, Andersen AN (2005) Imprinting diseases and IVF, Danish National IVF cohort study. Hum Reprod 20:950–954
DeBaun MR, Niemitz EL, Feinberg AP (2003) Association of in vitro fertilization with Beckwith–Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am J Hum Genet 72:156–160
Gicquel C, Gaston V, Mandelbaum J et al (2003) In vitro fertilization may increase the risk of Beckwith–Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene. Am J Hum Genet 72:1338–1341
Halliday J, Oke K, Breheny S et al (2004) Beckwith–Wiedemann syndrome and IVF, a case–control study. Am J Hum Genet 75:526–528
Chang A, Moley K, Feinberg A, Wangler M, DeBaun M (2005) The association between Beckwith–Weidemann syndrome and assisted reproductive technology, a case series of nineteen patients. Fertil Steril 83:349–354
Doornbos M, Maas S, McDonnell J, Vermeiden J, Hennekam R (2007) Infertility, assisted reproduction technologies and imprinting disturbances, a Dutch study. Hum Reprod 22(9):2476–2480
Sutcliffe A, Peters C, Bowdin S, Temple K, Reardon W, Wilson L, Clayton-Smith J, Brueton L, Bannister W, Maher E (2006) Assisted reproductive therapies and imprinting disorders – a preliminary British survey. Hum Reprod 21(4):1009–1011
Hansen M, Kurinczuk J, Bower C, Webb S (2002) The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med 346:725–730
Stromberg B, Dahlquist G, Ericson A et al (2002) Neurological sequelae in children born after in-vitro fertilisation, a population-based study. Lancet 359:461–465
Helmerhorst F, Perquin D, Donker D, Keirse M (2004) Perinatal outcome of singletons and twins after assisted conception, a systematic review of controlled studies. BMJ 328:261
Jackson RA, Gibson KA, Wu YW, Croughan MS (2004) Perinatal outcomes in singletons following in vitro fertilization, a meta-analysis. Obstet Gynecol 103:551–563
Bonduelle M, Wennerholm U, Loft A et al (2005) A multicentre cohort study of the physical health of 5-year-old children conceived after intracytoplasmic sperm injection, in vitro fertilization and natural conception. Hum Reprod 20:413–419
Klemetti R, Gissler M, Sevon T et al (2005) Children born after assisted fertilization have an increased rate of major congenital anomalies. Fertil Steril 84:1300–1307
Olson C, Keppler-Noreuil K, Romitti P et al (2005) In vitro fertilization is associated with an increase in major birth defects. Fertil Steril 84:1308–1315
Shevell T, Malone F, Vidaver J et al (2005) Assisted reproductive technology and pregnancy outcome. Obstet Gynecol 106:1039–1045
Helmerhorst F, Perquin D, Donker D, Keirse M (2004) Perinatal outcome of singletons and twins after assisted conception, a systematic review of controlled studies. BMJ 328:261
Jackson R, Gibson K, Wu Y, Croughan M (2004) Perinatal outcomes in singletons following in vitro fertilization, a meta-analysis. Obstet Gynecol 103:551–563
Doyle P, Beral V, Maconochie N (1992) Preterm delivery, low birthweight and small-for-gestational-age in liveborn singleton babies resulting from in-vitro fertilization. Hum Reprod 7:425–428
Wang J, Clark A, Kirby C et al (1994) The obstetric outcome of singleton pregnancies following in-vitro fertilization/gamete intra-fallopian transfer. Hum Reprod 9:141–146
Koudstaal J, Braat DD, Bruinse HW et al (2000) Obstetric outcome of singleton pregnancies after IVF, a matched control study in four Dutch university hospitals. Hum Reprod 15:1819–1825
Miles HL, Hofman PL, Peek J et al (2007) In vitro fertilization improves childhood growth and metabolism. J Clin Endocrinol Metab 92:3441–3445
Rinaudo P, Schultz R (2004) Effects of embryo culture on global pattern of gene expression in preimplantation mouse embryos. Reproduction 128:301–311
Katz-Jaffe M, Linck D, Schoolcraft W, Gardner D (2005) A proteomic analysis of mammalian preimplantation embryonic development. Reproduction 130:899–905
Corcoran D, Fair T, Park S, Rizos D, Patel O et al (2005) Suppressed expression of genes involved in transcription and translation in in vitro compared with in vivo cultured bovine embryos. Reproduction 131:651–660
Machaty Z, Day BN, Prather RS (1998) Development of early porcine embryos in vitro and in vivo. Biol Reprod 59:451–455
Farin P, Slenning B, Britt J (1999) Estimates of pregnancy outcomes based on selection of bovine embryos produced in vivo or in vitro. Theriogenology 52:659–670
Wang W, Abeydeera L, Han Y et al (1999) Morphologic evaluation and actin filament distribution in porcine embryos produced in vitro and in vivo. Biol Reprod 60:1020–1028
Khurana N, Niemann H (2000) Effects of cryopreservation on glucose metabolism and survival of bovine morulae and blastocysts derived in vitro or in vivo. Theriogenology 54:313–326
Montag M, Koll B, Holmes P, van der Ven H (2000) Significance of the number of embryonic cells and the state of the zona pellucida for hatching of mouse blastocysts in vitro versus in vivo. Biol Reprod 62:1738–1744
Holm P, Booth P, Callesen H (2002) Kinetics of early in vitro development of bovine in vivo- and in vitro-derived zygotes produced and/or cultured in chemically defined or serum-containing media. Reproduction 123:553–565
Papadopoulos S, Rizos D, Duffy P et al (2002) Embryo survival and recipient pregnancy rates after transfer of fresh or vitrified, in vivo or in vitro produced ovine blastocysts. Anim Reprod Sci 74:35–44
Rizos D, Ward F, Duffy P et al (2002) Consequences of bovine oocyte maturation, fertilization or early embryo development in vitro versus in vivo, implications for blastocyst yield and blastocyst quality. Mol Reprod Dev 61:234–248
Watkins A, Platt D, Papenbrock T et al (2007) Mouse embryo culture induces changes in postnatal phenotype including raised systolic blood pressure. Proc Natl Acad Sci USA 104:5449–5454
Giritharan G, Talbi S, Donjacour A et al (2007) Effect of in vitro fertilization on gene expression and development of mouse preimplantation embryos. Reproduction 134:63–72
Crosier AE, Farin PW, Dykstra MJ et al (2000) Ultrastructural morphometry of bovine compact morulae produced in vivo or in vitro. Biol Reprod 62:1459–1465
Crosier AE, Farin PW, Dykstra MJ et al (2001) Ultrastructural morphometry of bovine blastocysts produced in vivo or in vitro. Biol Reprod 64:1375–1385
Boni R, Tosti E, Roviello S, Dale B (1999) Intercellular communication in in vivo- and in vitro-produced bovine embryos. Biol Reprod 61:1050–1055
Abe H, Otoi T, Tachikawa S et al (1999) Fine structure of bovine morulae and blastocysts in vivo and in vitro. Anat Embryol (Berl) 199:519–527
Wrenzycki C, Herrmann D, Carnwath JW, Niemann H (1996) Expression of the gap junction gene connexin43 (Cx43) in preimplantation bovine embryos derived in vitro or in vivo. J Reprod Fertil 108:17–24
Eckert J, Niemann H (1998) mRNA expression of leukaemia inhibitory factor (LIF) and its receptor subunits glycoprotein 130 and LIF-receptor-beta in bovine embryos derived in vitro or in vivo. Mol Hum Reprod 4:957–965
Stojanov T, Alechna S, O’Neill C (1999) In-vitro fertilization and culture of mouse embryos in vitro significantly retards the onset of insulin-like growth factor-II expression from the zygotic genome. Mol Hum Reprod 5:116–124
Stojanov T, O’Neill C (2001) In vitro fertilization causes epigenetic modifications to the onset of gene expression from the zygotic genome in mice. Biol Reprod 64:696–705
Bertolini M, Beam SW, Shim H et al (2002) Growth, development, and gene expression by in vivo- and in vitro-produced day 7 and 16 bovine embryos. Mol Reprod Dev 63:318–328
Lazzari G, Wrenzycki C, Herrmann D et al (2002) Cellular and molecular deviations in bovine in vitro-produced embryos are related to the large offspring syndrome. Biol Reprod 67:767–775
Lighten AD, Moore GE, Winston RM, Hardy K (1998) Routine addition of human insulin-like growth factor-I ligand could benefit clinical in-vitro fertilization culture. Hum Reprod 13:3144–3150
Wang TH, Chang CL, Wu HM et al (2006) Insulin-like growth factor-II (IGF-II), IGF-binding protein-3 (IGFBP-3), and IGFBP-4 in follicular fluid are associated with oocyte maturation and embryo development. Fertil Steril 86:1392–1401
Kamat BR, Brown LF, Manseau EJ et al (1995) Expression of vascular permeability factor/vascular endothelial growth factor by human granulosa and theca lutein cells. Role in corpus luteum development. Am J Pathol 146:157–165
Gordon JD, Mesiano S, Zaloudek CJ, Jaffe RB (1996) Vascular endothelial growth factor localization in human ovary and fallopian tubes, possible role in reproductive function and ovarian cyst formation. J Clin Endocrinol Metab 81:353–359
Lam PM, Briton-Jones C, Cheung CK et al (2003) Vascular endothelial growth factor in the human oviduct, localization and regulation of messenger RNA expression in vivo. Biol Reprod 68:1870–1876
Torry D, Holt V, Keenan J, Harris G, Caudle M, Torry R (1996) Vascular endothelial growth factor expression in cycling human endometrium. Fertil Steril 66(1):72–80
Hornung D, Lebovic DI, Shifren JL et al (1998) Vectorial secretion of vascular endothelial growth factor by polarized human endometrial epithelial cells. Fertil Steril 69:909–915
Zhang L, Scott P, Turley H et al (1998) Validation of antivascular endothelial growth factor (anti-VEGF) antibodies for immunohistochemical localization of VEGF in tissue sections, expression of VEGF in the human endometrium. J Pathol 185:402–408
Sugino N, Kashida S, Karube-Harada A et al (2002) Expression of vascular endothelial growth factor (VEGF) and its receptors in human endometrium throughout the menstrual cycle and in early pregnancy. Reproduction 123:379–387
Watson R, Anthony F, Pickett M et al (1992) Reverse transcription with nested polymerase chain reaction shows expression of basic fibroblast growth factor transcripts in human granulosa and cumulus cells from in vitro fertilisation patients. Biochem Biophys Res Commun 187:1227–1231
Di Blasio AM, Vigano P, Cremonesi L et al (1993) Expression of the genes encoding basic fibroblast growth factor and its receptor in human granulosa cells. Mol Cell Endocrinol 96:R7–R11
Seli E, Zeyneloglu HB, Senturk LM et al (1998) Basic fibroblast growth factor, peritoneal and follicular fluid levels and its effect on early embryonic development. Fertil Steril 69:1145–1148
Salmassi A, Zhang Z, Schmutzler A et al (2005) Expression of mRNA and protein of macrophage colony-stimulating factor and its receptor in human follicular luteinized granulosa cells. Fertil Steril 83:419–425
Boehm K, Daimon M, Gorodeski I et al (1990) Expression of the insulin-like and platelet-derived growth factor genes in human uterine tissues. Mol Reprod Dev 27:93–101
Desai N, Goldfarb J (1996) Growth factor/cytokine secretion by a permanent human endometrial cell line with embryotrophic properties. J Assist Reprod Genet 13:546–550
Kauma S, Aukerman S, Eierman D, Turner T (1991) Colony-stimulating factor-1 and C-FMS expression in human endometrial tissues and placenta during the menstrual cycle and early pregnancy. J Clin Endocrinol Metab 73:746–751
Davis S, Krozowski Z, McLachlan R, Burger H (1987) Inhibin gene expression in the human corpus luteum. J Endocrinol 115:R21–R23
Wang H, Lu S, Han X et al (1992) Control of inhibin production by dispersed human luteal cells in vitro. Reprod Fertil Dev 4:67–75
He Z, Liu H, Mele C et al (1999) Expression of inhibin/activin subunits and their receptors and binding proteins in human preimplantation embryos. J Assist Reprod Genet 16:73–80
Vanttinen T, Liu J, Hyden-Granskog C et al (2000) Regulation of immunoreactive inhibin A and B secretion in cultured human granulosa-luteal cells by gonadotropins, activin A and insulin-like growth factor type-1 receptor. J Endocrinol 167:289–294
Petraglia F, Florio P, Luisi S et al (1998) Expression and secretion of inhibin and activin in normal and neoplastic uterine tissues. High levels of serum activin A in women with endometrial and cervical carcinoma. J Clin Endocrinol Metab 83:1194–1200
Ramasharma K, Li C (1987) Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells. Proc Natl Acad Sci USA 84:2643–2647
Muttukrishna S, Groome N, Ledger W (1997) Gonadotropic control of secretion of dimeric inhibins and activin A by human granulosa-luteal cells in vitro. J Assist Reprod Genet 14:566–574
Neulen J, Raczek S, Pogorzelski M et al (1998) Secretion of vascular endothelial growth factor/vascular permeability factor from human luteinized granulosa cells is human chorionic gonadotrophin dependent. Mol Hum Reprod 4:203–206
Chia C, Winston R, Handyside A (1995) EG, TGF-alpha and EGFR expression in human preimplantation embryos. Development 121:299–307
Smotrich D, Stillman R, Widra E et al (1996) Immunocytochemical localization of growth factors and their receptors in human preembryos and fallopian tubes. Hum Reprod 11:184–190
Jiang Q, Chen S, Xing F (2000) Expression of epidermal growth factor receptor in human preimplantation embryos. Zhonghua Fu Chan Ke Za Zhi 35:468–469
Chobotova K, Chobotova K, Spyropoulou I, Carver J et al (2002) Heparin-binding epidermal growth factor and its receptor ErbB4 mediate implantation of the human blastocyst. Mech Dev 119:137–144
Roudebush W, Purnell E, Stoddart N, Fleming S (2002) Embryonic platelet-activating factor, temporal expression of the ligand and receptor. J Assist Reprod Genet 19:72–78
Osterlund C, Wramsby H, Pousette A (1996) Temporal expression of platelet-derived growth factor (PGDF)-A and its receptor in human preimplantation embryos. Mol Hum Reprod 2(7):507–512
Freeman M, Whitworth C, Hill G (1995) Granulosa cell co-culture enhances human embryo development and pregnancy rate following in-vitro fertilization. Hum Reprod 10:408–414
Mansour R, Aboulghar M, Serour G, Abbass A (1994) Co-culture of human pronucleate oocytes with their cumulus cells. Hum Reprod 9:1727–1729
Quinn P, Margalit R (1996) Beneficial effects of coculture with cumulus cells on blastocyst formation in a prospective trial with supernumerary human embryos. J Assist Reprod Genet 13:9–14
Yeung W, Lau E, Chan S, Ho P (1996) Coculture with homologous oviductal cells improved the implantation of human embryos, a prospective randomized control trial. J Assist Reprod Genet 13:762–767
Kervancioglu M, Saridogan E, Atasu T et al (1997) Human fallopian tube epithelial cell co-culture increases fertilization rates in male factor infertility but not in tubal or unexplained infertility. Hum Reprod 12:1253–1258
Nieto F, Watkins W, Lopata A et al (1996) The effects of coculture with autologous cryopreserved endometrial cells on human in vitro fertilization and early embryo morphology, a randomized study. J Assist Reprod Genet 13:386–389
Ben-Chetrit A, Jurisicova A, Casper R (1996) Coculture with ovarian cancer cell enhances human blastocyst formation in vitro. Fertil Steril 65:664–666
Shapiro B, Richter K, Harris D, Daneshmand S (2001) A randomized controlled study comparing human embryo growth in sequential blastocyst media with or without Vero cell coculture. Fertil Steril 76:s3–s4
Menezo Y, Sakkas D (2002) Monozygotic twinning, is it related to apoptosis in the embryo? Hum Reprod 17:247–248
Behr B, Fisch J, Racowsky C, Miller K, Pool T, Milki A (2000) Blastocyst-ET and monozygotic twinning. J Assit Reprod Genet 17(6):349–351
Milki A, Jun S, Hinckley M, Behr B, Giudice L, Westphal L (2003) Incidence of monozygotic twinning with blastocyst transfer compared to cleavage-stage transfer. Fertil Steril 79(3):503–506
Wright V, Schieve L, Vahratian A, Reynolds M (2004) Monozygotic twinning associated with day 5 embryo transfer in pregnancies conceived after IVF. Hum Reprod 19(8):1831–1836
Desai N, Goldfarb J (1998) Co-cultured human embryos may be subjected to widely different microenvironments, pattern of growth factor/cytokine release by Vero cells during the co-culture interval. Hum Reprod 13:1600–1605
O’Neill C (1998) Autocrine mediators are required to act on the embryo by the 2-cell stage to promote normal development and survival of mouse preimplantation embryos in vitro. Biol Reprod 58:1303–1309
O’Neill C (1997) Evidence for the requirement of autocrine growth factors for development of mouse preimplantation embryos in vitro. Biol Reprod 56:229–237
Jin Y, Guo X, Li L et al (2001) The effect of autocrine factors on development of early embryos of mouse. Shi Yan Sheng Wu Xue Bao 34:77–80
Lighten A, Hardy K, Winston R, Moore G (1997) Expression of mRNA for the insulin-like growth factors and their receptors in human preimplantation embryos. Mol Reprod Dev 47:134–139
Punjabi U, Vereecken A, Delbeke L et al (1990) Embryo-derived platelet activating factor, a marker of embryo quality and viability following ovarian stimulation for in vitro fertilization. J In Vitro Fert Embryo Transf 7:321–326
Turpeenniemi-Hujanen T, Feinberg R, Kauppila A, Puistola U (1995) Extracellular matrix interactions in early human embryos, implications for normal implantation events. Fertil Steril 64:132–138
Hwu Y, Chen C, Li S et al (2006) Expression of vascular endothelial growth factor messenger ribonucleic acid and protein in human preimplantation embryos. Fertil Steril 85:1830–1832
Juriscova A, Casper R, MacLusky N, Mills G, Librach C (1996) HLA-G expression during preimplantation human embryo development. Proc Natl Acad Sci USA 93:161–165
Menicucci A, Noci I, Fuzzi B, Criscuoli L, Scarselli G, Barricordi O (1991) Nonclassic sHLA class I in human oocyte culture medium. Hum Immunol 60:1054–1057
Fuzzi B, Rizzo R, Criscuoli L, Noci I, Melchiorri L, Scarselli B et al (2002) HLA-G expression in early embryos is a fundamental prerequisite for the obtainment of pregnancy. Eur J Immunol 32(2):311–315
Gardner D, Sakkas D (2003) Assessment of embryo viability, the ability to select a single embryo for transfer – a review. Placenta 24:5–12
Noci I, Fuzzi B, Rizzo R, Melchiorri L, Criscuoli L, Diabizzi S et al (2005) Embryonic soluble HLA-G as a marker of developmental potential in embryos. Hum Reprod 20(1):138–146
Sher G, Keskintepe L, Nouriani M, Roussev R, Batzofin J (2004) Expression of sHLA-G in supernatants of individually cultured 46-h embryos, a potentially valuable indicator of “embryo competency” and IVF outcome. Reprod Biomed Online 9:74–78
Rebmann V, Switala M, Eue I, Grosse-Wilde H (2010) Soluble HLA-G is an independent factor for the prediction of pregnancy outcome after ART, a German multi-centre study. Hum Reprod 25(7):1691–1698
Desai N, Lawson J, Goldfarb J (2000) Assessment of growth factor effects on postthaw development of cryopreserved mouse morulae to the blastocyst stage. Hum Reprod 15:410–418
Desai N, Kattal N, AbdelHafez F et al (2007) Granulocyte–macrophage colony stimulating factor (GM-CSF) and co-culture can affect post thaw development and apoptosis in cryopreserved embryos. J Assist Reprod Genet 24:215–222
O’Neill C, Ryan J, Collier M et al (1989) Supplementation of in-vitro fertilisation culture medium with platelet activating factor. Lancet 2:769–772
Borini A, Bulletti C, Cattoli M et al (1997) Use of recombinant leukemia inhibitory factor in embryo implantation. Ann N Y Acad Sci 828:157–161
Kim D, Kim M, Kang H et al (2001) The supplementation of granulocyte–macrophage colony-stimulating factor (GM-CSF) in culture medium improves the pregnancy rate in human ART programs. Fertil Steril 76:s6
Shapiro B, Richter K, Daneshmand S et al (2003) Granulocyte–macrophage colony-stimulating factor enhances human embryo development to the blastocyst stage, a randomized study. Fertil Steril 79:15–16
Huang J, Mehrens D, Wiese R et al (2001) High-throughput genomic and proteomic analysis using microarray technology. Clin Chem 47:1912–1916
Soulet D, Rivest S (2002) Perspective, how to make microarray, serial analysis of gene expression, and proteomic relevant to day-to-day endocrine problems and physiological systems. Endocrinology 143:1995–2001
Arici A, Engin O, Attar E, Olive D (1995) Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in human endometrium. J Clin Endocrinol Metab 80:1908–1915
Cullinan E, Abbondanzo S, Anderson P et al (1996) Leukemia inhibitory factor (LIF) and LIF receptor expression in human endometrium suggests a potential autocrine/paracrine function in regulating embryo implantation. Proc Natl Acad Sci USA 93:3115–3120
Tsai H, Chang C, Hsieh Y, Lo H (2000) Leukemia inhibitory factor expression in different endometrial locations between fertile and infertile women throughout different menstrual phases. J Assist Reprod Genet 17:415–418
Sato A, Bo M, Otani T, Mochizuki M (1995) Expression of epidermal growth factor, transforming growth factor-alpha and epidermal growth factor receptor messenger RNA in human endometrium and endometrial carcinoma. Nippon Sanka Fujinka Gakkai Zasshi 47:473–478
Zhao Y, Chegini N (1999) The expression of granulocyte–macrophage-colony stimulating factor (GM-CSF) and receptors in human endometrium. Am J Reprod Immunol 42:303–311
Yoo H, Barlow D, Mardon H (1997) Temporal and spatial regulation of expression of heparin-binding epidermal growth factor-like growth factor in the human endometrium, a possible role in blastocyst implantation. Dev Genet 21:102–108
Leach R, Khalifa R, Ramirez N et al (1999) Multiple roles for heparin-binding epidermal growth factor-like growth factor are suggested by its cell-specific expression during the human endometrial cycle and early placentation. J Clin Endocrinol Metab 84:3355–3363
Stavreus-Evers A, Aghajanova L, Brismar H et al (2002) Co-existence of heparin-binding epidermal growth factor-like growth factor and pinopodes in human endometrium at the time of implantation. Mol Hum Reprod 8:765–769
Tang X, Rossi M, Masterson B, Chegini N (1994) Insulin-like growth factor I (IGF-I), IGF-I receptors, and IGF binding proteins 1–4 in human uterine tissue, tissue localization and IGF-I action in endometrial stromal and myometrial smooth muscle cells in vitro. Biol Reprod 50:1113–1125
Giudice L, Dsupin B, Jin I et al (1993) Differential expression of messenger ribonucleic acids encoding insulin-like growth factors and their receptors in human uterine endometrium and decidua. J Clin Endocrinol Metab 76:1115–1122
Giudice L, Lamson G, Rosenfeld R, Irwin J (1991) Insulin-like growth factor-II (IGF-II) and IGF binding proteins in human endometrium. Ann N Y Acad Sci 626:295–307
Morishige K, Kurachi H, Amemiya K et al (1993) Menstrual stage-specific expression of epidermal growth factor and transforming growth factor-alpha in human oviduct epithelium and their role in early embryogenesis. Endocrinology 133:199–207
Chegini N, Zhao Y, McLean F (1994) Expression of messenger ribonucleic acid and presence of immunoreactive proteins for epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha) and EGF/TGF alpha receptors and 125I-EGF binding sites in human fallopian tube. Biol Reprod 50:1049–1058
Kurachi H, Morishige K, Imai T et al (1994) Expression of epidermal growth factor and transforming growth factor-alpha in fallopian tube epithelium and their role in embryogenesis. Horm Res 41(Suppl 1):48–154
Pfeifer T, Chegini N (1994) Immunohistochemical localization of insulin-like growth factor (IGF-I), IGF-I receptor, and IGF binding proteins 1–4 in human fallopian tube at various reproductive stages. Biol Reprod 50:281–289
Keltz M, Attar E, Buradagunta S et al (1996) Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in the human fallopian tube. Am J Obstet Gynecol 175:1611–1619
Lam P, Briton-Jones C, Cheung C et al (2003) Vascular endothelial growth factor in the human oviduct, localization and regulation of messenger RNA expression in vivo. Biol Reprod 68:1870–1876
Sugino N, Kashida S, Takiguchi S et al (2000) Expression of vascular endothelial growth factor and its receptors in the human corpus luteum during the menstrual cycle and in early pregnancy. J Clin Endocrinol Metab 85:3919–3924
Familiari G, Verlengia C, Nottola S et al (1996) Heterogeneous distribution of fibronectin, tenascin-C, and laminin immunoreactive material in the cumulus-corona cells surrounding mature human oocytes from IVF-ET protocols – evidence that they are composed of different subpopulations, an immunohis-tochemical study using scanning confocal laser and fluorescence microscopy. Mol Reprod Dev 43:392–402
Piccinni M, Scaletti C, Mavilia C et al (2001) Production of IL-4 and leukemia inhibitory factor by T cells of the cumulus oophorus, a favorable microenvironment for preimplantation embryo development. Eur J Immunol 31:2431–2437
Neulen J, Yan Z, Raczek S et al (1995) Human chorionic gonadotropin-dependent expression of vascular endothelial growth factor/vascular permeability factor in human granulosa cells, importance in ovarian hyperstimulation syndrome. J Clin Endocrinol Metab 80:1967–1971
Zolti M, Ben-Rafael Z, Meirom R, Shemesh M, Bider D, Mashiach S, Apte R (1991) Cytokine involvement in occytes and early embryos. Fertil Steril 56(2):265–272
Sjoblom C, Wikland M, Robertson S (2002) Granulocyte–macrophage colony-stimulating factor (GM-CSF) acts independently of the beta common subunit of the GM-CSF receptor to prevent inner cell mass apoptosis in human embryos. Biol Reprod 67:1817–1823
Sharkey A, Dellow K, Blayney M et al (1995) Stage-specific expression of cytokine and receptor messenger ribonucleic acids in human preimplantation embryos. Biol Reprod 53:974–981
van Eijk M, Mandelbaum J, Salat-Baroux J et al (1996) Expression of leukaemia inhibitory factor receptor subunits LIFR beta and gp130 in human oocytes and preimplantation embryos. Mol Hum Reprod 2:355–360
Wanggren K, Lalitkumar P, Hambiliki F et al (2007) Leukaemia inhibitory factor receptor and gp130 in the human fallopian tube and endometrium before and after mifepristone treatment and in the human preimplantation embryo. Mol Hum Reprod 13:391–397
Quinn P, Margalit R (1996) Beneficial effects of coculture with cumulus cells on blastocyst formation in a prospective trial with supernumerary human embryos. J Assist Reprod Genet 13:9–14
Wiemer K, Cohen J, Wiker S et al (1989) Coculture of human zygotes on fetal bovine uterine fibroblasts, embryonic morphology and implantation. Fertil Steril 52:503–508
Tucker M, Ingargiola P, Massey J et al (1994) Assisted hatching with or without bovine oviductal epithelial cell co-culture for poor prognosis in-vitro fertilization patients. Hum Reprod 9:1528–1531
Hu Y, Maxson W, Hoffman D et al (1998) Co-culture with assisted hatching of human embryos using buffalo rat liver cells. Hum Reprod 13:165–168
Schillaci R, Ciriminna R, Cefalu E (1994) Vero cell effect on in-vitro human blastocyst development, preliminary results. Hum Reprod 9:1131–1135
Magli M, Gianaroli L, Ferraretti A et al (1995) Human embryo co-culture, results of a randomized prospective study. Int J Fertil Menopausal Stud 40:254–259
Turner K, Lenton E (1996) The influence of Vero cell culture on human embryo development and chorionic gonadotrophin production in vitro. Hum Reprod 11:1966–1974
Harvey M, Kaye P (1992) Insulin-like growth factor-1 stimulates growth of mouse preimplantation embryos in vitro. Mol Reprod Dev 31:195–199
Lin T, Yen J, Gong K et al (2003) IGF-1/IGFBP-1 increases blastocyst formation and total blastocyst cell number in mouse embryo culture and facilitates the establishment of a stem-cell line. BMC Cell Biol 4:14
Kim S, Lee G, Lee S et al (2005) Embryotropic effect of insulin-like growth factor (IGF)-I and its receptor on development of porcine preimplantation embryos produced by in vitro fertilization and somatic cell nuclear transfer. Mol Reprod Dev 72:88–97
Kim S, Lee S, Kim J et al (2006) Antiapoptotic effect of insulin-like growth factor (IGF)-I and its receptor in porcine preimplantation embryos derived from in vitro fertilization and somatic cell nuclear transfer. Mol Reprod Dev 73:1523–1530
Herrler A, Krusche C, Beier H (1998) Insulin and insulin-like growth factor-I promote rabbit blastocyst development and prevent apoptosis. Biol Reprod 59:1302–1310
Byrne A, Southgate J, Brison D, Leese H (2002) Regulation of apoptosis in the bovine blastocyst by insulin and the insulin-like growth factor (IGF) super-family. Mol Reprod Dev 62:489–495
Makarevich A, Markkula M (2002) Apoptosis and cell proliferation potential of bovine embryos stimulated with insulin-like growth factor I during in vitro maturation and culture. Biol Reprod 66:386–392
Moreira F, Paula-Lopes F, Hansen P et al (2002) Effects of growth hormone and insulin-like growth factor-I on development of in vitro derived bovine embryos. Theriogenology 57:895–907
Sirisathien S, Hernandez-Fonseca H, Brackett B (2003) Influences of epidermal growth factor and insulin-like growth factor-I on bovine blastocyst development in vitro. Anim Reprod Sci 77:21–32
Palma G, Muller M, Brem G (1997) Effect of insulin-like growth factor I (IGF-I) at high concentrations on blastocyst development of bovine embryos produced in vitro. J Reprod Fertil 110:347–353
Block J, Drost M, Monson R et al (2003) Use of insulin-like growth factor-I during embryo culture and treatment of recipients with gonadotropin-releasing hormone to increase pregnancy rates following the transfer of in vitro-produced embryos to heat-stressed, lactating cows. J Anim Sci 81:1590–1602
Mitchell M, Swanson R, Hodgen G, Oehninger S (1994) Enhancement of in vitro murine embryo development by recombinant leukemia inhibitory factor. J Soc Gynecol Investig 1:215–219
Lavranos T, Rathjen P, Seamark R (1995) Trophic effects of myeloid leukaemia inhibitory factor (LIF) on mouse embryos. J Reprod Fertil 105:331–338
Mezhevikina L, Fedorova V, Kapralova I, Fesenko E (2006) Increased survival of preimplantation mouse embryos in medium with recombinant cytokine LIF. Ontogenez 37:55–62
Fry R, Batt P, Fairclough R, Parr R (1992) Human leukemia inhibitory factor improves the viability of cultured ovine embryos. Biol Reprod 46:470–474
Ptak G, Lopes F, Matsukawa K et al (2006) Leukaemia inhibitory factor enhances sheep fertilization in vitro via an influence on the oocyte. Theriogenology 65:1891–1899
de Moraes A, Hansen P (1997) Granulocyte–macrophage colony-stimulating factor promotes development of in vitro produced bovine embryos. Biol Reprod 57:1060–1065
Robertson S, Sjoblom C, Jasper M et al (2001) Granulocyte–macrophage colony-stimulating factor promotes glucose transport and blastomere viability in murine preimplantation embryos. Biol Reprod 64:1206–1215
Papayannis M, Eyheremendy V, Sanjurjo C, Blaquier J, Raffo F (2007) Effect of granulocyte–macrophage colony stimulating factor on growth, resistance to freezing and thawing and re-expansion of murine blastocysts. Reprod Biomed Online 14(1):96–101
Behr B, Mooney S, Wen Y, Polan M, Wang H (2005) Preliminary experience with low concentration of granulocyte–macrophage colony-stimulating factor, a potential regulator in preimplantation mouse embryo development and apoptosis. J Assist Reprod Genet 22(1):25–32
Bhatnagar P, Papaioannou V, Biggers J (1995) CSF-1 and mouse preimplantation development in vitro. Development 121:1333–1339
Tamada H, Higashiyama C, Takano H et al (1999) The effects of heparin-binding epidermal growth factor-like growth factor on preimplantation-embryo development and implantation in the rat. Life Sci 64:1967–1973
Lim J, Lee D, Song H et al (2006) Heparin-binding epidermal growth factor (HB-EGF) may improve embryonic development and implantation by increasing vitronectin receptor (integrin alphanubeta3) expression in peri-implantation mouse embryos. J Assist Reprod Genet 23:111–119
Lim K, Jang G, Ko K et al (2007) Improved in vitro bovine embryo development and increased efficiency in producing viable calves using defined media. Theriogenology 67:293–302
Aflafo E, Sod-Moriah U, Potashnik G, Har-Vardi I (2007) EGF increases expression and activity of Pas in perimplantation rat embryos and their implantation rate. Reprod Biol Endocrinol 29(5):4
Shi H, Miller F, Miller K, Kim M (1992) The effect of platelet activating factor on different phases of murine in vitro fertilization. J Assist Reprod Genet 9:373–377
Roudebush W, Duralia D, Butler W (1996) Effect of platelet-activating factor (PAF) on preimplantation mouse B6D2F1/J embryo formation. Am J Reprod Immunol 35:272–276
Zhou P, Liu D, Cang M et al (2008) TGFalpha and EGFR in ovine preimplantation embryos and effects on development. Anim Reprod Sci 104:370–381
Taniguchi F, Harada T, Yoshida S et al (1998) Paracrine effects of bFGF and KGF on the process of mouse blastocyst implantation. Mol Reprod Dev 50:54–62
Dunglison G, Barlow D, Sargent I (1996) Leukaemia inhibitory factor significantly enhances the blastocyst formation rates of human embryos cultured in serum-free medium. Hum Reprod 11:191–196
Hsieh Y, Tsai H, Chang C, Hsu L, Chang S, Lo H (2000) Prolonged culture of human cryopreserved embryos with recombinant human leukemia inhibitory factor. J Assist Reprod Genet 17(3):131–134
Spanos S, Becker D, Winston R, Hardy K (2000) Anti-apoptotic action of insulin-like growth factor-I during human preimplantation embryo development. Biol Reprod 63(5):1413–1420
Sjoblom C, Wikland M, Robertson S (1999) Granulocyte–macrophage colony-stimulating factor promotes human blastocyst development in vitro. Hum Reprod 14: 3069–3076
Martin K, Barlow D, Sargent I (1998) Heparin-binding epidermal growth factor significantly improves human blastocyst development and hatching in serum-free medium. Hum Reprod 13:1645–1652
Khamsi F, Armstrong D, Zhang X (1996) Expression of urokinase-type plasminogen activator in human preimplantation embryos. Mol Hum Reprod 2:273–276
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media New York
About this protocol
Cite this protocol
Hegde, A., Behr, B. (2012). Media Composition: Growth Factors. In: Smith, G., Swain, J., Pool, T. (eds) Embryo Culture. Methods in Molecular Biology, vol 912. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-971-6_11
Download citation
DOI: https://doi.org/10.1007/978-1-61779-971-6_11
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-970-9
Online ISBN: 978-1-61779-971-6
eBook Packages: Springer Protocols