Advertisement

Journal of Assisted Reproduction and Genetics

, Volume 30, Issue 3, pp 293–303 | Cite as

New insights into human pre-implantation metabolism in vivo and in vitro

  • Yves Ménézo
  • Isabelle Lichtblau
  • Kay Elder
Review

Abstract

The metabolism of pre-implantation embryos is far from being understood. In human embryos, the two major obstacles are the scarcity of material, for obvious ethical reasons, and complete absence of a relevant in vivo control model. Over-extrapolation from animal species to human systems adds to the complexity of the problem. Removal of some metabolites from media has been proposed, such as glucose and essential amino acids, on the basis of their pseudo “toxicity”. In contrast, addition of some compounds such as growth factors has been proposed in order to decrease apoptosis, which is a natural physiologic process. These suggestions reflect the absence of global knowledge, and in consequence mask reality. Some aspects of metabolism have been ignored, such as lipid metabolism. Others are seriously underestimated, such as oxidative stress and its relationship to imprinting/methylation, of paramount importance for genetic regulation and chromosomal stability. It has become increasingly obvious that more studies are essential, especially in view of the major extension of ART activities worldwide.

Keywords

Human embryo Metabolism Imprinting Oxidative stress Culture medium 

References

  1. 1.
    Whitten WK. Culture of tubal mouse ova. Nature. 1956;177:96.PubMedCrossRefGoogle Scholar
  2. 2.
    Brinster RL. Studies on the development of mouse embryos in vitro I the effect of osmolarity and hydrogen ion concentration. J Exp Zool. 1965;158:49–57.PubMedCrossRefGoogle Scholar
  3. 3.
    Brinster RL. Studies on the development of mouse embryos in vitro II. The effect of energy sources. J Exp Zool. 1965;158:59–68.PubMedCrossRefGoogle Scholar
  4. 4.
    Brinster RL. Studies on the development of mouse embryos in vitro III the effect of fixed nitrogen source. J Exp Zool. 1965;158:69–77.PubMedCrossRefGoogle Scholar
  5. 5.
    Brinster RL. In vitro culture of mammalian embryos. J Anim Sci. 1968;27 Suppl 1:1–14.PubMedGoogle Scholar
  6. 6.
    Whittingham DG. Culture of mouse ova. J Reprod Fertil Suppl. 1971;14:7–21.PubMedGoogle Scholar
  7. 7.
    Tervit HR, Whittingham D, Rowson LEA. Successful culture in vitro of sheep and cattle ova. J Reprod Fertil. 1972;20:493–7.Google Scholar
  8. 8.
    Ménézo Y. Milieu synthétique pour la survie et la maturation des gamètes et pour la culture de l’œuf fécondé. CR Acad Sci D Paris. 1976;282:1967–70.Google Scholar
  9. 9.
    Ao A, Erickson RP, Winston RM, Handyside AH. Transcription of paternal Y-linked genes in the human zygote as early as the pronucleate stage. Zygote. 1994;2:281–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Lopes S, Jurisicova A, Casper RF. Gamete-specific DNA fragmentation in unfertilized human oocytes after intracytoplasmic sperm injection. Hum Reprod. 1998;13:703–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Ménézo Y, Dale B, Cohen M. DNA damage and repair in human oocytes and embryos: a review. Zygote. 2010;18:357–65.PubMedCrossRefGoogle Scholar
  12. 12.
    Betteridge KJ, Rieger D. Embryo transfer and related techniques in domestic animals, and their implications for human medicine. Hum Reprod. 1993;8:147–67.PubMedGoogle Scholar
  13. 13.
    Ho Y, Doherty AS, Schultz RM. Mouse preimplantation embryo embryo development in vitro: effect of sodium concentration in culture media on RNA synthesis and accumulation and gene expression. Mol Reprod Dev. 1994;38:131–41.PubMedCrossRefGoogle Scholar
  14. 14.
    Jung T. Protein synthesis and degradation in non-cultured and in vitro cultured rabbit blastocysts. J Reprod Fertil. 1989;86:507–12.PubMedCrossRefGoogle Scholar
  15. 15.
    Wrenzycki C, Herrmann D, Carnwath JW, Niemann H. Alterations in the relative abundance of gene transcripts in preimplantation bovine embryos cultured in medium supplemented with either serum or PVA. Mol Reprod Dev. 1999;53:8–18.PubMedCrossRefGoogle Scholar
  16. 16.
    Hiura H, Okae H, Miyauchi N, Sato F, Sato A, Van De Pette M, et al. Characterization of DNA methylation errors in patients with imprinting disorders conceived by assisted reproduction technologies. Hum Reprod. 2012;27:2541–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Naglee DL, Maurer RR, Foote RH. Effect of osmolarity on in vitro development of rabbit embryos in a chemically defined medium. Exp Cell Res. 1969;58:331–3.PubMedCrossRefGoogle Scholar
  18. 18.
    Ménézo YJ, Hérubel F. Mouse and bovine models for human IVF. Reprod Biomed Online. 2002;4:170–5.PubMedCrossRefGoogle Scholar
  19. 19.
    Liu Z, Foote RH. Sodium chloride, osmolytes, and osmolarity effects on blastocyst formation in bovine embryos produced by in vitro fertilization (IVF) and cultured in simple serum-free media. J Assist Reprod Genet. 1996;13:562–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Kane MT. Bicarbonate requirements for culture of one-cell rabbit ova to blastocysts. Biol Reprod. 1975;12:552–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Gomes Sobrinho DB, Oliveira JB, Petersen CG, Mauri AL, Silva LF, Massaro FC, et al. IVF/ICSI outcomes after culture of human embryos at low oxygen tension: a meta-analysis. Reprod Biol Endocrinol. 2011;9:143–54.PubMedCrossRefGoogle Scholar
  22. 22.
    Guérin P, El Mouatassim S, Ménézo Y. Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update. 2001;7:175–89.PubMedCrossRefGoogle Scholar
  23. 23.
    Martín-Romero FJ, Miguel-Lasobras EM, Domínguez-Arroyo JA, González-Carrera E, Alvarez IS. Contribution of culture media to oxidative stress and its effect on human oocytes. Reprod Biomed Online. 2008;17:652–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Wales RG, Brinster RL. The uptake of hexoses by mouse pre-implantation embryos in vitro. J Reprod Fertil. 1968;15:415–22.PubMedCrossRefGoogle Scholar
  25. 25.
    Schini, Bavister BD. Two-cell block to development of cultured hamster embryos is caused by phosphate and glucose. Biol Reprod. 1988;39:1183–92.PubMedCrossRefGoogle Scholar
  26. 26.
    Chatot CL, Ziomek CA, Bavister BD, Lewis JL, Torres I. An improved culture medium supports development of random-bred 1-cell mouse embryos in vitro. J Reprod Fertil. 1989;86:679–88.PubMedCrossRefGoogle Scholar
  27. 27.
    Biggers JD, McGinnis LK. Evidence that glucose is not always an inhibitor of mouse preimplantation development in vitro. Hum Reprod. 2001;16:153–63.PubMedCrossRefGoogle Scholar
  28. 28.
    Pampfer S. Apoptosis in rodent peri-implantation embryos: differential susceptibility of inner cell mass and trophectoderm cell lineages—a review. Placenta. 2000;21(suppltA):S3–10.PubMedCrossRefGoogle Scholar
  29. 29.
    Jimenez A, Madrid-Bury N, Fernandez R, Pérez-Garnelo S, Moreira P, Pintado B, et al. Hyperglycemia-induced apoptosis affects sex ratio of bovine and murine preimplantation embryos. Mol Reprod Dev. 2003;65:180–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Cassuto G, Chavrier M, Menezo Y. Culture conditions and not prolonged culture time are responsible for monozygotic twinning in human in vitro fertilization. Fertil Steril. 2003;80:462–3.PubMedCrossRefGoogle Scholar
  31. 31.
    Ménézo Y, Khatchadourian C. Implication of glucose 6 phosphate isomerase (EC 5.3.1.9) activity in blocking segmentation of the mouse ovum at the 2 cell stage in vitro. CR Acad Sci. 1990;310:297–301.Google Scholar
  32. 32.
    Ludwig TE, Lane M, Bavister BD. Differential effect of hexoses on hamster embryo development in culture. Biol Reprod. 2001;64:1366–74.PubMedCrossRefGoogle Scholar
  33. 33.
    Downs SM, Mosey JL, Klinger J. Fatty acid oxidation and meiotic resumption in mouse oocytes. Mol Reprod. Dev. 2009; 76:844–53.Google Scholar
  34. 34.
    Dunning KR, Akison LK, Russell DL, Norman RJ, Robker RL. Increased beta-oxidation and improved oocyte developmental competence in response to L-carnitine during ovarian in vitro follicle development in mice. Biol Reprod. 2011;85:548–55.PubMedCrossRefGoogle Scholar
  35. 35.
    Dunning KR, Cashman K, Russell DL, Thompson JG, Norman RJ, Robker RL. Beta-oxidation is essential for mouse oocyte developmental competence and early embryo development. Biol Reprod. 2010;83:909–18.PubMedCrossRefGoogle Scholar
  36. 36.
    Waterman RA, Wall RJ. Lipid interactions with in vitro development of mammalian zygotes. Gamete Res. 1988;21:243–54.PubMedCrossRefGoogle Scholar
  37. 37.
    Hillman N, Flynn TJ. The metabolism of exogenous fatty acids by preimplantation mouse embryos developing in vitro. J Embryol Exp Morphol. 1980;56:157–68.PubMedGoogle Scholar
  38. 38.
    Ferguson EM, Leese HJ. A potential role for triglyceride as an energy source during bovine oocyte maturation and early embryo development. Mol Reprod Dev. 2006;73:1195–201.PubMedCrossRefGoogle Scholar
  39. 39.
    Homa ST, Racowsky C, McGaughey RW. Lipid analysis of immature pig oocytes. J Reprod Fertil. 1986;77:425–34.PubMedCrossRefGoogle Scholar
  40. 40.
    Flynn TJ, Hillman N. Lipid synthesis from [U14C]glucose in pre-implantation mouse embryos in culture. Biol Reprod. 1978;19:922–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Ménézo Y, Renard JP, Delobel B, Pageaux JF. Kinetic study of fatty acid composition of day 7 to day 14 cow embryos. Biol Reprod. 1982;26:787–90.PubMedCrossRefGoogle Scholar
  42. 42.
    Montjean D, Entezami F, Lichtblau I, Belloc S, Gurgan T, Menezo Y. Carnitine content in the follicular fluid and expression of the enzymes involved in beta oxidation in oocytes and cumulus cells. J Assist Reprod Genet. 2012;29:1221–5.PubMedCrossRefGoogle Scholar
  43. 43.
    Abdelrazik A, El-Damen H, Badrawi R, Sharma A. Agarwal Introduction of a single step medium from fertilization through blastocyst stage by supplementation of the culture media with L-Carnitine. ASRM meeting, Washington DC; 2007. p. 312.Google Scholar
  44. 44.
    Casslén BG. Free amino acids in human uterine fluid. Possible role of high taurine concentration. J Reprod Med. 1987;32:181–4.PubMedGoogle Scholar
  45. 45.
    Dawson KM, Baltz JM. Organic osmolytes and embryos: substrates of the Gly and beta transport systems protect mouse zygotes against the effects of raised osmolarity. Biol Reprod. 1997;56:1550–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Baltz JM. Media composition: salts and osmolality. Methods Mol Biol. 2012;912:61–80.PubMedGoogle Scholar
  47. 47.
    Khatchadourian C, Guillaud J, Menezo Y. Interactions in glycine and methionine uptake, conversion and incorporation into proteins in the preimplantation mouse embryo. Zygote. 1994;2:301–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Summers MC, Biggers JD. Chemically defined media and the culture of mammalian preimplantation embryos: historical perspective and current issues. Hum Reprod Update. 2003;9:557–82.PubMedCrossRefGoogle Scholar
  49. 49.
    Guyader-Joly C, Khatchadourian C, Ménézo Y. Comparative glucose and fructose incorporation and conversion by in vitro produced bovine embryos. Zygote. 1996;4:85–91.PubMedCrossRefGoogle Scholar
  50. 50.
    Brison DR, Houghton FD, Falconer D, Roberts SA, Hawkhead J, Humpherson PG, et al. Identification of viable embryos in IVF by non-invasive measurement of amino acid turnover. Hum Reprod. 2004;19:2319–24.PubMedCrossRefGoogle Scholar
  51. 51.
    Ménézo Y, Testart J, Perone D. Serum is not necessary in human in vitro fertilization, early embryo culture, and transfer. Fertil Steril. 1984;42:750–5.PubMedGoogle Scholar
  52. 52.
    Tay JI, Rutherford AJ, Killick SR, Maguiness SD, Partridge RJ, Leese HJ. Human tubal fluid: production, nutrient composition and response to adrenergic agents. Hum Reprod. 1997;12:2451–6.PubMedCrossRefGoogle Scholar
  53. 53.
    De Groot N, Hochberg A. Gene imprinting during placental and embryonic development. Mol Reprod Dev. 1993;36:390–406.CrossRefGoogle Scholar
  54. 54.
    Goshen R, Ben Rafael Z, Gonik B, Lustig O, Tannos V, de-Groot N, et al. The role of genomic imprinting in implantation. Fertil Steril. 1994;2:903–10.Google Scholar
  55. 55.
    Khosla S, Dean W, Reik W. Culture of pre-implantation embryos and its long-term effects on gene expression and phenotype. Hum Reprod Updat. 2001;7:419–27.CrossRefGoogle Scholar
  56. 56.
    Ménézo Y, Khatchadourian C, Gharrib A, Hamidi J, Sarda N. Regulation of sadenosyl methionine synthesis in the mouse embryo. Life Sci. 1989;44:1601–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Benkhalifa M, Montjean D, Cohen-Bacrie P, Ménézo Y. Imprinting: RNA expression for ho mocysteine recycling in the human oocyte. Fertil Steril. 2010;93:1585–90.PubMedCrossRefGoogle Scholar
  58. 58.
    Niemitz EL, Feinberg AP. Epigenetics and assisted reproductive technology: a call for investigation. Am J Hum Genet. 2004;74:599–609.PubMedCrossRefGoogle Scholar
  59. 59.
    Wolff GL, Kodell RL, Moore SR, Cooney CE. Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/mice. FASEB J. 1998;12:949–57.PubMedGoogle Scholar
  60. 60.
    Xin Z, Tachibana M, Guggiari, et al. Role of histone methyltransferase G9a in CpG methylation of the Prader–Willi syndrome imprinting centre. J Biol Chem. 2003;278:14996–5000.PubMedCrossRefGoogle Scholar
  61. 61.
    Hoffman M. Hypothesis: hyperhomocysteinemia is an indicator of oxidant stress. Med Hypotheses. 2011;77:1088–93.PubMedCrossRefGoogle Scholar
  62. 62.
    Ménézo Y, Mares P, Cohen M, Brack M, Viville S, Elder K. Autism, imprinting and epigenetic disorders: a metabolic syndrome linked to anomalies in homocysteine recycling starting in early life?? J Assist Reprod Genet. 2011;28:1143–5.PubMedCrossRefGoogle Scholar
  63. 63.
    Lu S, Hoestje SM, Choo E, Epner DE. Induction of caspase dependant and independant apoptosis in response to methionine restriction. Int J Oncol. 2003;22:415–20.PubMedGoogle Scholar
  64. 64.
    Guérin P, Ménézo Y. Hypotaurine and taurine in gamete and embryo environments: de novo synthesis via the cysteine sulfinic acid pathway in oviduct cells. Zygote. 1995;3:333–43.PubMedCrossRefGoogle Scholar
  65. 65.
    Dumoulin JC, van Wissen LC, Menheere PP, Michiels AH, Geraedts JP, Evers JL. Taurine acts as an osmolyte in human and mouse oocytes and embryos. Biol Reprod. 1997;56:739–44.PubMedCrossRefGoogle Scholar
  66. 66.
    Gardner DK, Lane M. Amino acids and ammonium regulate mouse embryo development in culture. Biol Reprod. 1993;48:377–85.PubMedCrossRefGoogle Scholar
  67. 67.
    Elhassan YM, Wu G, Leanez AC, et al. Amino acid concentrations in fluids from the bovine oviduct and uterus and in KSOM-based culture media. Theriogenology. 2001;55:1907–18.PubMedCrossRefGoogle Scholar
  68. 68.
    Katari S, Turan N, Bibikova M, Erinle O, Chalian R, Foster M, et al. DNA methylation and gene expression differences in children conceived in vitro or in vivo. Hum Mol Genet. 2009;18:3769–78.PubMedCrossRefGoogle Scholar
  69. 69.
    Pike IL, Murdoch RN, Wales RG. The incorporation of carbon dioxide into the major classes of RNA during culture of the preimplantation mouse embryo. J Reprod Fertil. 1975;45:211–2.PubMedCrossRefGoogle Scholar
  70. 70.
    Badouard C, Ménézo Y, Panteix G, Ravanat JL, Douki T, Cadet J, et al. Determination of new types of DNA lesions in human sperm. Zygote. 2008;16:9–13.PubMedCrossRefGoogle Scholar
  71. 71.
    Zenzes MT, Puy LA, Bielecki R. Immunodetection of benzo[a]pyrene adducts in ovarian cells of women exposed to cigarette smoke. Mol Hum Reprod. 1998;4:159–65.PubMedCrossRefGoogle Scholar
  72. 72.
    Wachsman JT. DNA methylation and the association between genetic and epigenetic changes: relation to carcinogenesis. Mutat Res. 1997;375:1–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Ménézo YJR, Russo G, Tosti E, El Mouatassim S, Benkhalifa M. Expression profile of genes coding for DNA repair in human oocytes using pangenomic microarrays, with a special focus on ROS linked decays. J Assist Reprod Genet. 2007;24:513–20.PubMedCrossRefGoogle Scholar
  74. 74.
    Epstein CJ. Gene expression and macromolecular synthesis during pre-implantation embryonic development. Biol Reprod. 1975;12:82–105.PubMedCrossRefGoogle Scholar
  75. 75.
    Olson SE, Seidel Jr GE. Culture of in vitro-produced bovine embryos with vitamin E improves development in vitro and after transfer to recipients. Biol Reprod. 2000;62:248–52.PubMedCrossRefGoogle Scholar
  76. 76.
    Giustarini D, Dalle-Donne I, Colombo R, Milzani A, Rossi R. Is ascorbate able to reduce disulfide bridges? A cautionary note. Nitric Oxide. 2008;19:252–8.PubMedCrossRefGoogle Scholar
  77. 77.
    Bavister BD, Leibfried ML, Lieberman G. Development of preimplantation embryos of the golden hamster in a defined culture medium. Biol Reprod. 1983;28:235–47.PubMedCrossRefGoogle Scholar
  78. 78.
    Tsai FC, Gardner DK. Nicotinamide, a component of complex culture media, inhibits mouse embryo development in vitro and reduces subsequent developmental potential after transfer. Fertil Steril. 1994;61:376–82.PubMedGoogle Scholar
  79. 79.
    O’Neill C. Endogenous folic acid is essential for normal development of preimplantation embryos. Hum Reprod. 1998;13:1312–6.PubMedCrossRefGoogle Scholar
  80. 80.
    Ménézo Y, Entezami F, Lichtblau I, Belloc S, Cohen M, Dale B. Oxidative stress and fertility: incorrect assumptions and ineffective solutions? Zygote. 2012;12:1–11.CrossRefGoogle Scholar
  81. 81.
    Caro CM, Trounson A. Successful fertilization, embryo development, and pregnancy in human in vitro fertilization (IVF) using a chemically defined culture medium containing no protein. J In Vitro Fert Embryo Transf. 1986;3:215–7.PubMedCrossRefGoogle Scholar
  82. 82.
    Menezo Y, Khatchadourian C. Peptides bound to albumin. Life Sci. 1986;39:1751–3.PubMedCrossRefGoogle Scholar
  83. 83.
    Croteau S, Menezo Y. Growth factors: from oocyte maturation to blastocyst. Contracept Fertil Sex. 1994;22:648–55.PubMedGoogle Scholar
  84. 84.
    Richter KS. The importance of growth factors for preimplantation embryo development and in-vitro culture. Curr Opin Obstet Gynecol. 2008;20:292–304.PubMedCrossRefGoogle Scholar
  85. 85.
    Ménézo YJ, Servy E, Veiga A, Hazout A, Elder K. Culture systems: embryo co-culture. Methods Mol Biol. 2012;912:231–47.PubMedGoogle Scholar
  86. 86.
    Paria BC, Dey SK. Preimplantation embryo development in vitro: cooperative interactions among embryos and the role of growth factors. Proc Natl Acad Sci USA. 1990;87:4756–60.PubMedCrossRefGoogle Scholar
  87. 87.
    Gopichandran N, Leese HJ. The effect of paracrine/autocrine interactions on the in vitro culture of bovine preimplantation embryos. Reprod. 2006;131:269–67.CrossRefGoogle Scholar
  88. 88.
    O’Neill C. Evidence for the requirement of autocrine growth factors for development of mouse—preimplantation embryos in vitro. Biol Reprod. 1997;56:229–37.PubMedCrossRefGoogle Scholar
  89. 89.
    Desai NN, Goldfarb JM. Growth factor/cytokine secretion by a permanent human endometrial cell line with embryotrophic properties. J Assist Reprod Genet. 1996;13:546–50.PubMedCrossRefGoogle Scholar
  90. 90.
    Desai NN, Goldfarb J. 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. 1998;13:1600–5.PubMedCrossRefGoogle Scholar
  91. 91.
    Patrizio P, Sakkas D. From oocyte to baby: a clinical evaluation of the biological efficiency of in vitro fertilization. Fertil Steril. 2009;91:1061–6.PubMedCrossRefGoogle Scholar
  92. 92.
    Menezo Y, Guerin P. Preimplantation embryo metabolism and embryo interaction with the in vitro environment. In: Elder K, Cohen J, editors. Human preimplantation Embryo evaluation and selection. London: Taylor-Francis; 2007. p. 191–200.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Laboratoire CLEMENTParisFrance
  2. 2.London Fertility AssociatesHarley StreetLondonUK
  3. 3.Clinique de la MuetteParisFrance
  4. 4.Bourn Hall ClinicCambridgeUK

Personalised recommendations