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Retinoid metabolism in the embryo

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Vitamin A and Retinoids: An Update of Biological Aspects and Clinical Applications

Part of the book series: MCBU Molecular and Cell Biology Updates ((MCBU))

Abstract

In 1982, isotretinoin (Accutane) was marketed as an agent for treatment of acne. As early as 1983, Franz Rosa, MD, an official of the Federal Drug Administration (FDA), reported five cases of malformations associated with use of Accutane in pregnancy [1]. The malformations were major and included hydrocephalus, cardiovascular and ear defects [2 3]. By the most recent estimates available, malformations in a total of 94 human infants have been associated with prenatal Accutane exposure [4]. In contrast with the number of reported cases, the US FDA estimates that 900-1300 retinoid-exposed babies were born with severe birth defects in the first five years after Accutane was marketed. Because the drug is still commercially available, the Teratology Society has strongly recommended that women of childbearing age using the drug should practice contraception and that use of this drug should be thoroughly monitored [5].

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References

  1. Rosa FW (1983) Teratogenicity of isotretinoin. Lancet 2: 513

    Article  PubMed  CAS  Google Scholar 

  2. Braun JT, Franciosi RA, Mastri AR, Drake RM, O’Niel BL (1984) Isotretinoin dysmorphic syndrome. Lancet 1: 506–507

    Article  PubMed  CAS  Google Scholar 

  3. Lammer EJ, Chen DT, Hoar RM, Agnish ND, Benke PJ, Braun JT, Curry CJ, Fernhoff PM, Grix AW, Lott IT et al (1985) Retinoic acid embryopathy. New Engl J Med 313: 837–841

    Article  PubMed  CAS  Google Scholar 

  4. Schardein JL (1993) Human studies: Retinoic Acid Embryopathy. In:JL Shardein (ed.): Chemically Induced Birth Defects. Marcel Dekker, New York, 558–567

    Google Scholar 

  5. Teratology Society (1991) Recommendations for Isotretinoin use in woman of childbearing potential. Teratology 44: 1–6

    Article  Google Scholar 

  6. Creech Kraft J, Slikker Jr, W, Bailey JR, Roberts LG, Fischer B, Wittfoht W, Nau H (1991) Plasma pharmacokinetics of 13-cis- and all-trans-retinoic acid in the Cynomolgus monkey and the identification of the conjugate metabolites 13-cis and all-trans-retinoyl-(3-glucuronides: a comparison to one human case study with Isotretinoin. Drug Metab Dispos 19: 317–324

    Google Scholar 

  7. Creech Kraft J, Nau H, Lammer E, Olney A (1989) Embryonic retinoid concentrations after maternal intake of Isotretinoin. New Engl J Med 321: 262

    Google Scholar 

  8. Creech Kraft J, Shepard T, Juchau MR (1993) Tissue levels of retinoids in human embryo/fetuses unexposed to AccutaneR. Reprod Toxicol 7: 11–15

    Article  Google Scholar 

  9. Kochhar DM, Penner JD, Tellone C (1984) Comparative teratogenic activities of two retinoids: Effects on palate and limb development. Teratogen Carcinogen Mutagen 4: 377–387

    Article  CAS  Google Scholar 

  10. Creech Kraft J, Kochhar DM, Scott WJJr, Nau H (1987) Low teratogenicity of 13-cis-retinoic acid (isotretinoin) in the mouse corresponds to low embryo concentrations during organogenesis: comparison to the all-trans isomer. Toxicol Appl Pharmacol 87: 474–482

    Article  Google Scholar 

  11. Creech Kraft J, Lofberg B, Chahoud I, Bochert G, Nau H (1989) Teratogenicity and placental transfer of all- trans 13-cis 4-oxo-all-trans, and 4-oxo-13-cis-retinoic acid after a low oral dose during organogenesis in mice. Toxicol Appl Pharmacol 100: 162–176

    Article  PubMed  CAS  Google Scholar 

  12. Creech Kraft J, Eckhoff Chr Kochhar DM, Bochert G, Chahoud I, Nau H (1991) Isotretinoin (13-cis-retinoic acid), metabolism cis-trans isomerization, glucuronidation and transfer to the mouse embryo: Consequences for teratogenicity. Teratogen Carcinogen Mutagen 11: 21–30

    Article  CAS  Google Scholar 

  13. Willhite CC, Wier PJ, Berry D (1989) Dose response and structure activity considerations in retinoic-induced dysmorphogenesis. Crit Rev Toxicol 20: 113–135

    Article  PubMed  CAS  Google Scholar 

  14. Kochhar DM, Penner J (1987) Developmental effects of Isotretinoin and 4-oxo-Isotretinoin: The role of metabolism in teratogenicity. Teratology 36: 67–75

    Article  PubMed  CAS  Google Scholar 

  15. Satre MA, Penner JD, Kochhar DM (1989) Pharmacokinetic assessment of teratologically effective concentrations of an endogenous retinoic acid metabolite. Teratology 39: 341–348

    Article  PubMed  CAS  Google Scholar 

  16. Gunning DB, Barua AB, Olson JA (1993) Comparative teratogenicity and metabolism of all-trans-retinoic acid, all-trans-retinoyl-13-glucose and all-trans-retinoyl-13-glucuronide in pregnant Sprague Dawly rats. Teratology 47: 29–36

    Article  PubMed  CAS  Google Scholar 

  17. Lee QP, Juchau MR, Creech Kraft J (1991) Microinjection of cultured rat embryos: studies with retinal, 13- cis- and all-trans-retinoic acid. Teratology 44: 313–323

    Article  PubMed  CAS  Google Scholar 

  18. Creech Kraft J, Bechter R, Lee QP, Juchau MR (1992) Microinjections of cultured rat conceptuses: Studies with 4-oxo-all-trans-retinoic acid, 4-oxo-13-cis-retinoic acid and all-trans-retinoyl43-glucuronide. Teratology 45: 259–270

    Article  Google Scholar 

  19. Creech Kraft J, Juchau MR (1992) Correlations between conceptal concentrations of all-trans retinoic acid and dysmorphogenesis after microinjections of all-trans-retinoic acid, 13-cis-retinoic acid, all-trans retinoyl-(3-glucuronide or retinol in cultured whole rat embryos. Drug Metab Dispos 20: 218–225

    Google Scholar 

  20. Creech Kraft J, Bui T, Juchau MR (1992) Elevated levels of all-trans-retinoic acid in cultured rat embryos 1.5 h after microinjections with 13-cis-retinoic acid or retinol and correlations with dysmorphogenesis. Biochem Pharmacol 44:R 21–24

    Google Scholar 

  21. Creech Kraft J, Juchau MR (1992) Conceptal biotransformation of 4-oxo-all-trans-retinoic acid, 4-oxo-13cis-retinoic acid and all-trans-retinoyl-13-glucuronide in rat whole embryo culture. Biochem Pharmacol 43: 2289–2292

    Article  PubMed  CAS  Google Scholar 

  22. Creech Kraft J, Juchau MR (1993) 9-cis-Retinoic acid: a direct-acting dysmorphogen. Biochem Pharmacol 46: 709–716

    Article  Google Scholar 

  23. Pekovich M, Brand NJ, Krust A, Chambon P (1987) A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 330: 444–450

    Article  Google Scholar 

  24. Brand NJ, Petkovich M, Krust A, Chambon P, de The Machio A, Tiollais P, Dejean A (1988) Identification of a second human retinoic acid receptor. Nature 332: 850–853

    Article  PubMed  CAS  Google Scholar 

  25. Krust A, Kastner P, Petkovich M, Zelent A, Chambon P (1989) A third human retinoic acid receptor, hRAR-a. Proc Natl Acad Sci USA 86: 5210–5214

    Article  Google Scholar 

  26. Giguere V, Ong ES, Sequi P, Evans R (1987) Identification of a receptor for morphogen retinoic acid. Nature 330: 624–629

    Article  PubMed  CAS  Google Scholar 

  27. Allenby G, Bocquel M-T, Saunders M, Kazmer S, Speck J, Rosenberger M, Lovey A, Kastner P, Grippo J, Chambon P et al (1993) Retinoic acid receptors and retinoic X receptors: Interactions with endogenous retinoic acids. Proc Natl Acad Sci USA 90: 30–34

    Article  PubMed  CAS  Google Scholar 

  28. Apfel C, Crettaz M, LeMotte P (1992) Differential binding and activation of synthetic retinoids to retinoic acid receptors. In: G Morriss-Kay (ed.): Retinoids in Normal Development and Teratogenesis. Oxford University Press, Oxford, 65–74

    Google Scholar 

  29. Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, Thaller C (1992) 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 68: 397–406

    CAS  Google Scholar 

  30. Levin AA, Sturzenbecker LJ, Kazmer S, Bosakowski T, Huselton C, Allenby G, Speck J, Kratzeisen C, Rosenberger M, Lovey A et al (1992) 9-Cis retinoic acid stereoisomer binds and activates the nuclear receptor RXRa. Nature 355: 359–361

    CAS  Google Scholar 

  31. Lu HC, Eichele G, Thaller C (1997) Ligand-bound RXR can mediate retinoid signal transduction during embryogenesis. Development 124: 195–203

    PubMed  CAS  Google Scholar 

  32. Thaller C, Eichele G (1987) Identification and spatial distribution of retinoids in the developing chick limb bud. Nature 327: 625–628

    Article  PubMed  CAS  Google Scholar 

  33. Thaller C, Eichele G (1990) Isolation of 3,4-didehyhdroretinoic acid, a novel morphogenetic in the chick limb bud. Nature 345: 815–819

    Article  PubMed  CAS  Google Scholar 

  34. Scott WJ, Walter R, Tzimas G, Sass JO, Nau H, Collins M (1994) Endogenous status of retinoids and their cytosolic binding proteins in limb buds of chick versus mouse embryos. Dev Biol 165: 397–409

    Article  PubMed  CAS  Google Scholar 

  35. Horton C, Maden M (1995) The endogenous distribution of retinoids during normal development and teratogenesis in mouse embryo. Develop Dyn 202: 312–323

    Article  CAS  Google Scholar 

  36. Durston AJ, Timmermans WJ, Hage HFJ, deVries NJ, Heideveld M, Nieuwkoop PD (1989) Retinoic acid causes an anteroposterior transformation in the developing central nervous system. Nature 340: 140–144

    Article  PubMed  CAS  Google Scholar 

  37. Creech Kraft J, Schuh T, Juchau MR, Kimelman D (1994) The retinoid X receptor 9-cis retinoic acid, is a potential regulator of early Xenopus development. Proc Natl Acad Sci USA 91: 3067–3071

    Article  Google Scholar 

  38. Pijnappel WWM, Hendriks HFJ, Folkers GE, van den Brink CE, Dekker EJ, Edellenbosch C, van der Saag PT, Durston AJ (1993) The retinoid ligand 4-oxo-retinoic acid is a highly active modulator of positional specification. Nature 366: 340–344

    Article  PubMed  CAS  Google Scholar 

  39. Creech Kraft J, Schuh T, Juchau J, Kimelman D (1994) Temporal distribution, localization and metabolism of retinol, didehydroretinol and retinal during development. Biochem J 301: 111–119

    PubMed  CAS  Google Scholar 

  40. Azuma M, Seki T, Fujishita S (1990) Changes of egg retinoids during the development of Xenopus laevis Vision Res 30: 1395–1400

    Article  CAS  Google Scholar 

  41. Blumberg B, Bolado Jr, J, Derguini F, Craig AG, Moreno T, Chakravarti D, Heyman R, Buck J, Evans R (1996) Novel retinoic acid receptor ligands in Xenopus embryos Proc Natl Acad Sci USA 93: 4873–4878

    CAS  Google Scholar 

  42. Costaridis P, Horton C, Zeitlinger J, Holder N, Maden M (1996) Endogenous retinoids in Zebrafish embryo and adult. Develop Dyn 205: 41–51

    Article  CAS  Google Scholar 

  43. Buck J, Gruen F, Derguini F, Chen Y, Kimura S, Noy N, Haemmerling U (1993) Anhydroretinol: A natually occurring inhibitor of lymphocyte physiology. J Exp Med 178: 1675–1680

    Article  Google Scholar 

  44. Derguini F, Nakanishi K, Haemmerling U (1994) Synthesis and intracellular signalling activity of (14R), (14S) and 14RS)-14-Hydroxy-4,14-Retro-Retinol (14-HRR). Biochemistry 33: 623–628

    Article  PubMed  CAS  Google Scholar 

  45. Derguini F, Nakanishi K, Buck J, Haemmerling U, Omen F (1994) Spectroscopic studies of anhydroretinol, an endogenous mammalian and insect retro-retinoid. Angew Chem Int Ed Eng 33: 1837–1839

    Article  Google Scholar 

  46. Chen Y-P, Huang L, Russo A, Solursch M (1992) Retinoic acid is enriched in Hensen’s node and is developmentally regulated in the early chicken embryo. Proc Natl Acad Sci USA 89: 7194–7197

    Article  Google Scholar 

  47. Minucci S, Saint-Jeannet J-P, Toyanna R, Scita G, DeLuca LM, Taira M, Levin AA, Ozato K, Dawid IB (1996) Retinoid X receptor ligands produce malformations in Xenopus embryos. Proc Natl Acad Sci USA 93: 1803–1807

    Article  PubMed  CAS  Google Scholar 

  48. Hogan BLM, Thaller C, Eichele G (1992) Evidence that Hensen’s node is a site of retinoic acid synthesis. Nature 359: 237–241

    Article  PubMed  CAS  Google Scholar 

  49. McCaffery P, Draeger U (1994) Hot spots of retinoic acid synthesis in the developing spinal cord. Proc Natl Acad Sci USA 91: 7194–7197

    Article  PubMed  CAS  Google Scholar 

  50. Maden M, Gale E, Zile M (1998) The role of vitamin A in the development of the central nervous system. Am Soc Nutr Sci 471S–475S

    Google Scholar 

  51. Helms J, Thaller C, Eichele G (1994) Relationship between retinoic acid and sonic hedgehog, two polarizing signals in the chick wing bud. Development 120: 3267–3274

    PubMed  CAS  Google Scholar 

  52. Helms J, Kim CH, Eichele G, Thaller C (1996) Retinoic acid signalling is required during chick limb development. Development 122: 1385–1394

    PubMed  CAS  Google Scholar 

  53. Lu H-C, Revelli J-P, Goering L, Thaller C, Eichele G (1997) Retinod signalling is required for the establishment of a ZPA and for the expression of Hoxb-8 a mediator of ZPA formation. Development 124: 1643–1651

    PubMed  CAS  Google Scholar 

  54. Schuh TJ, Hall BL, Creech Kraft JM, Privalsky ML, Kimelman D (1993) V-erbA and citral reduce the teratogenic effects of all-trans retinoic acid and retinol, respectively, in Xenopus embryogenesis. Development 119: 785–798

    PubMed  CAS  Google Scholar 

  55. Bavik C, Ward S, Ong D (1997) Identification of a mechanism to localize generation of retinoic acid in rat embryos. Development 69: 155–167

    CAS  Google Scholar 

  56. Zheng WL, Ong DE (1998) Spatial and temporal patterns of expression of cellular retinol-binding protein and cellular retinoic acid-binding proteins in rat uterus during early pregnancy. Biol Reprod 58: 963–970

    Article  PubMed  CAS  Google Scholar 

  57. Johansson S, Gustafson AL, Donovan M, Romert A, Eriksson U, Dencker L (1997) Retinoid binding proteins in mouse yolk sac and chorio-allantoic placentas. Anat Embryol (Berl) 195: 483–490

    Article  CAS  Google Scholar 

  58. Ward SJ, Chambon P, Ong D, Bavik C (1997) A retinol-binding protein receptor-mediated mechanism for uptake of vitamin A to post implantation rat embryos. Biol Reprod 57: 751–755

    Article  PubMed  CAS  Google Scholar 

  59. Deuster G (1998) Alcohol Dehydrogenase as a Critical Mediator of Retinoic Acid Syhthesis from Vitamin A in the Mouse Embryo. Am Soc Nutr Sci 98: 459S–462S

    Google Scholar 

  60. Romert A, Tuvendal P, Simon A, Dencker L, Eriksson U (1998) The identification of a 9-cis retinol dehydrogenase in the mouse embryo reveals a pathway for 9-cis retinoic acid. Proc Natl Acad Sci USA 94: 4404–4409

    Article  Google Scholar 

  61. Mertz JR, Shang E, Piantedosi R, Wei S, Wolgemuth DJ, Blaner WS (1997) Identification and characterization of a stereospecific human enzyne that catalyzes 9-cis-retinol oxidation. A possible role in 9-cis retinoic acid formation. J Biol Chem 272: 11744–11749

    Article  PubMed  CAS  Google Scholar 

  62. Ang HW, Duester G (1997) Initiation of Retinoid Signalling in Primitive Streak Mouse Embryos: Spatiotemporal Expression Patterns of Receptors and Metabolic Enzymes for Ligand Synthesis Develop Dyn 208: 536–543

    Article  CAS  Google Scholar 

  63. Ang HL, Deltour L, Hayamizu TF, Zgombic-Knight M, Deuster G (1996) Retinoc acid synthesis in the mouse during gastrulation and craniofacial development linked to calss IV alcohol dehydrogenase gene expression. Biol Chem 271: 9526–9534

    Article  CAS  Google Scholar 

  64. Haselbeck R, Ang HL, Deltour L, Deuster G (1997) Retinoic acid and alcohol/retinol dehydrogenase in the mouse adrenal gland: A potential source of retinoic acid during development. Endocrinology 138: 3035–3041

    Article  PubMed  CAS  Google Scholar 

  65. McCaffery P, Draeger UC (1993) Retinoic acid synthesis in the developing retina. Adv Exp Med Biol 328: 181–190

    Article  PubMed  CAS  Google Scholar 

  66. McCaffery P, Lee M-O, Wagner MA, Sladek NE, Draeger UC (1992) Asymmetrical retinoic acid synthesis in the dorso-ventralmaxis of the retina. Development 115: 371–382

    PubMed  CAS  Google Scholar 

  67. McCaffery P, Posh KC, Napoli JL, Gudas L, Draeger UC (1993) Changing patterns of retinoic acid synthesis in the retina. Dev Biol 158: 390–399

    Article  CAS  Google Scholar 

  68. McCaffery P, Tempst P, Lara G, Draeger UC (1991) Aldehyde dehydrogenase is a positional marker in the retina. Development 112: 693–701

    PubMed  CAS  Google Scholar 

  69. Marsh-Armstrong N, McCaffery P, Dowling JE, Gilbert W, Draeger UC (1994) Retinoic acid is necessary for development of the ventral retina in zebrafish. Proc Natl Acad Sci USA 91: 7286–7290

    Article  PubMed  CAS  Google Scholar 

  70. Hyatt GA, Schmitt EA, Marsh-Armstrong NA, Dowling JE (1992) Retinoic acid-induced duplication of the zebrafish retina. Proc Natl Acad Sci USA 89: 8293–8297

    Article  PubMed  CAS  Google Scholar 

  71. Ray WJ, Bain G, Yao M, Gottlieb DI (1997) CYP26, a novel mammalian cytochrome P450, is induced by retinoic acid and defines a new family. J Biol Chem 272: 18702–18708

    Article  PubMed  CAS  Google Scholar 

  72. Sive H, Draper B, Harland RM, Weintraub H (1990) Identification of a retinoic acid sensitive period during axis formation in Xenopus laevis. Gene Develop 4: 932–942

    CAS  Google Scholar 

  73. Creech Kraft J, Juchau MR (1995) Xenopus laevis: A Model System for the study of embryonic retinoid metabolism. HI. Isomerization and metabolism of all-trans-retinoic acid and 9-cis-retinoic acid and their dysmorphogenic effects in embryos during neurulation. Drug Metab Dispos 23: 1058–1072

    Google Scholar 

  74. Leid M, Kastner P, Lyons R, Nakshatri N, Saunders M, Zacharewski T, Chen J-Y, Staub A, Gamier J-M Mader S et al (1992) Purification, cloning and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell 68: 377–395

    Article  PubMed  CAS  Google Scholar 

  75. Yu VC, Delsert C, Anderson B, Holloway JM, Devary O, Naeaer AM, Kim SY, Boulin J-M, Glass CK, Rosenfeld MG (1991) RXR13: A coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell 67: 1251–1266

    Article  PubMed  CAS  Google Scholar 

  76. Kastner P, Grondona J, Mark M, Gansmuller A, LeMeur M, Decimo D, Vonesch J-L, Dolle P, Chambon P (1994) Genetic analysis of RXRa developmental function: convergence of RXR and RAR signalling pathways in heart and eye morphogenesis. Cell 78: 987–1003

    Article  PubMed  CAS  Google Scholar 

  77. Creech Kraft J, Kimelman D, Juchau MR (1995) Xenopus laevis: A Model System for the Study of Retinoid Metabolism 1. Embryonic metabolism of 9-cis- and all-trans-retinals and retinols to their corresponding acid forms Drug Metab Dispos 23: 72–82

    Google Scholar 

  78. Collins M, Tzimas G, Humrnler H, Buergin H, Nau H (1994) Comparative teratology and transplacental pharmacokinetics of all-trans-retinoic acid, 13-cis-retinoic acid and retinyl palmitate following daily administration in rats. Toxicol Appl Pharmacol 127: 132–144

    Article  PubMed  CAS  Google Scholar 

  79. Collins M, Tzimas G, Burgin H, Hummler H, Nau H (1995) Single versus multiple dose administration of alltrans-retinoic acid during organogenesis: differential metabolism and transplacental kinetics in rat and rabbit. Toxicol Appl Pharmacol 130: 9–18

    Article  PubMed  CAS  Google Scholar 

  80. Creech Kraft J, Kimelman D, Juchau MR (1995) Xenopus laevis: A Model System for the Study of Retinoid Metabolism 2. Embryonic metabolism of all-trans-3,4-didehydroretinol to all-trans-3,4-didehydroretinoic acid. Drug Metab Dispos 23: 83–89

    CAS  Google Scholar 

  81. Eckhoff C, Chari S, Kromka M, Staudner H, Juhasz Rudiger H, Agnish N (1994) Teratogenicity and transplacental pharmacokinetics of 13-cis-retinoic acid in rabbits. Toxicol Appl Pharmacol 125: 34–41

    Article  PubMed  CAS  Google Scholar 

  82. Frolik CA, Roller P, Roberts AB, Sporn MB (1980) In vitro and in vivo metabolism of all-trans and 13-cis retinoic acid in hamsters. Identification of 13-cis-4-oxo-retinoic acid. J Biol Chem 255: 8057–8062

    CAS  Google Scholar 

  83. Kahn JR, Wells MJ, Hill D (1984) Effects of phenobarbital, 3-methylcholanthrene, and retinoid pretreatment on disposition of orally administered retinoids in mice. Drug Metab Dipos 12: 63–67

    Google Scholar 

  84. Sandberg JA, Eckhoff C, Nau H, Slikker W (1994) Pharmacokinetics of 13-cis- all-trans-,13-cis-4-oxo-, and all-trans-4-oxo-retinoic acid after intravenous administration in the Cynomolgus monkey. Drug Metab Dispos 22: 154–160

    PubMed  CAS  Google Scholar 

  85. Urbach J, Rando RR (1994) Isomerization of all-trans-retinoic acid to 9-cis-retinoic acid. Biochem J 299: 459–465

    PubMed  CAS  Google Scholar 

  86. Morriss-Kay GM (1993) Retinoic acid and craniofacial development: molecules and morphogenesis. Bioessays 15: 9–15

    Article  PubMed  CAS  Google Scholar 

  87. Avantaggiato V, Acampora D, Tuorto F, Simeone A (1996) Retinoic acid induces stage specific repatteming of the rostral central nervous system. Dev Biol 175: 347–357

    Article  PubMed  CAS  Google Scholar 

  88. Cunningham ML, MacAuley A, Mirkes PE (1994) From gastrulation to neurulation: transition in retinoic acid sensitivity identifies distinct stages of neural patterning in the rat. Develop Dyn 200: 227–241

    Article  CAS  Google Scholar 

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    J. M. Creech Kraft

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  1. Cattedra di Chimica Biologica, Istituto di Farmacologia e Farmacognosia, UniversitĂ  di Palermo, Via Forlanini 1, Palermo, I-90134, Italy

    Maria A. Livrea

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Creech Kraft, J.M. (2000). Retinoid metabolism in the embryo. In: Livrea, M.A. (eds) Vitamin A and Retinoids: An Update of Biological Aspects and Clinical Applications. MCBU Molecular and Cell Biology Updates. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8454-9_9

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  • DOI: https://doi.org/10.1007/978-3-0348-8454-9_9

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