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Impact of Oxidative Stress on Development

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Perinatal and Prenatal Disorders

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Abstract

The developing embryo and fetus, collectively termed the conceptus, are highly susceptible to the adverse effects of oxidative stress initiated by endogenous processes and by xenobiotics that enhance the formation of reactive oxygen species (ROS). This susceptibility is due in part to the high conceptal rates of cellular division and differentiation, and the complex processes involved in the formation of organ structures and development of functional systems, including brain activity. Alterations in these processes can result in in utero or perinatal death, or structural and functional birth defects, termed “teratogenesis.” The instability of ROS, and particularly hydroxyl radicals, means that proximate formation of ROS within the conceptus, rather than distal maternal formation, plays a critical role in teratogenesis. Susceptibility is compounded by relatively high levels of embryonic and fetal enzymes involved in ROS formation and xenobiotic bioactivation to free radical intermediates and conversely low levels of protective antioxidative enzymes. Enhanced ROS levels can adversely affect development by altering signal transduction and/or by oxidatively damaging conceptal cellular macromolecules such as lipids, proteins, and DNA, the latter of which may be mitigated by DNA repair enzymes. The risk of teratogenesis is therefore largely determined at the conceptal level, wherein mouse models littermates with an unfavorable imbalance among pathways of ROS formation and detoxification, and DNA repair, exhibit greater structural and/or functional birth defects than littermates with a favorable balance.

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References

  1. Abramov JP, Tran A, Shapiro AM, Wells PG. Protective role of endogenous catalase in baseline and phenytoin-enhanced neurodevelopmental and behavioral deficits initiated in utero and in aged mice. Reprod Toxicol. 2012;33:361–73.

    CAS  PubMed  Google Scholar 

  2. Abramov JP, Wells PG. Embryonic catalase protects against endogenous and phenytoin-enhanced DNA oxidation and embryopathies in acatalasemic and human catalase-expressing mice. FASEB J. 2011;25:2188–200.

    CAS  PubMed  Google Scholar 

  3. Abramov JP, Wells PG. Embryoprotective role of endogenous catalase in acatalasemic and human catalase-expressing mouse embryos exposed in culture to developmental and phenytoin-enhanced oxidative stress. Toxicol Sci. 2011;120:428–38.

    CAS  PubMed  Google Scholar 

  4. Albano E, Tomasi A, Goria-Gatti L, Dianzani MU. Spin trapping of free radical species produced during the microsomal metabolism of ethanol. Chem Biol Interact. 1988;65:223–34.

    CAS  PubMed  Google Scholar 

  5. Arlen RR, Wells PG. Inhibition of thalidomide teratogenicity by acetylsalicylic acid: evidence for prostaglandin H synthase-catalyzed bioactivation of thalidomide to a teratogenic reactive intermediate. J Pharmacol Exp Ther. 1996;277:1649–58.

    CAS  PubMed  Google Scholar 

  6. Azarbayjani F, Borg LAH, Danielsson BR. Increased susceptibility to phenytoin teratogenicity: excessive generation of reactive oxygen species or impaired antioxidant defense? Basic Clin Pharmacol Toxicol. 2006;99:305–11.

    CAS  PubMed  Google Scholar 

  7. Bassi C, Ho J, Srikumar T, Dowling RJO, Gorrini C, Miller SJ, Mak TW, Neel BG, Raught B, Stambolic V. Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress. Science. 2013;341:395–9.

    CAS  PubMed  Google Scholar 

  8. Bhuller Y, Jeng W, Wells PG. Variable in vivo embryoprotective role for ataxia-telangiectasia-mutated against constitutive and phenytoin-enhanced oxidative stress in atm knockout mice. Toxicol Sci. 2006;93:146–55.

    CAS  PubMed  Google Scholar 

  9. Bhuller Y, Wells PG. A developmental role for ataxia-telangiectasia mutated in protecting the embryo from spontaneous and phenytoin-enhanced embryopathies in culture. Toxicol Sci. 2006;93:156–63.

    CAS  PubMed  Google Scholar 

  10. Cantone I, Fisher AG. Epigenetic programming and reprogramming during development. Nat Struct Mol Biol. 2013;20:282–9.

    CAS  PubMed  Google Scholar 

  11. Chan K, Lu R, Chang JC, Kan YW. Proc Natl Acad Sci U S A. 1996;93:13943–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Chen CS, Squire JA, Wells PG. Reduced tumorigenesis in p53 knockout mice exposed in utero to low-dose vitamin E. Cancer. 2009;115:1563–75.

    CAS  PubMed  Google Scholar 

  13. Chen CS, Wells PG. Enhanced tumorigenesis in p53 knockout mice exposed in utero to high-dose vitamin E. Carcinogenesis. 2006;27:1358–68.

    CAS  PubMed  Google Scholar 

  14. Dennery PA. Effects of oxidative stress on embryonic development. Birth Defects Res C Embryo Today. 2002;81:155–62.

    Google Scholar 

  15. DeSesso JM. Amelioration of teratogenesis. I. Modification of hydroxyurea-induced teratogenesis by the antioxidant propyl gallate. Teratology. 1981;24:19–35.

    CAS  PubMed  Google Scholar 

  16. Devi BG, Schenker S, Mazloum B, Henderson GI. Ethanol-induced oxidative stress and enzymatic defenses in cultured fetal rat hepatocytes. Alcohol. 1996;13:327–32.

    CAS  PubMed  Google Scholar 

  17. Dong J, Sulik KK, S-y C. Nrf2-mediated transcriptional induction of antioxidant response in mouse embryos exposed to ethanol in vivo: implications for the prevention of fetal alcohol spectrum disorders. Antioxid Redox Signal. 2008;10:2023–33.

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Dong J, Sulik KK, S-y C. The role of NOX enzymes in ethanol-induced oxidative stress and apoptosis in mouse embryos. Toxicol Lett. 2010;193:94–100.

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Eriksson UJ, Borg LA. Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro. Diabetologia. 1991;34:325–31.

    CAS  PubMed  Google Scholar 

  20. Fantel AG, Person RE. Further evidence for the role of free radicals in the limb teratogenicity of L-NAME. Teratology. 2002;66:24–32.

    CAS  PubMed  Google Scholar 

  21. Hagay ZJ, Weiss Y, Zusman I, Peled-Kamar M, Reece EA, Eriksson UJ, Groner Y. Prevention of diabetes-associated embryopathy by overexpression of the free radical scavenger copper zinc superoxide dismutase in transgenic mouse embryos. Am J Obstet Gynecol. 1995;173: 1036–41.

    CAS  PubMed  Google Scholar 

  22. Hales BF. Modification of the teratogenicity and mutagenicity of cyclophosphamide with thiol compounds. Teratology. 1981;23:373–81.

    CAS  PubMed  Google Scholar 

  23. Hales BF, Brown H. The effect of in vivo glutathione depletion with buthionine sulfoximine on rat embryo development. Teratology. 1991;44:251–7.

    CAS  PubMed  Google Scholar 

  24. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press; 2007.

    Google Scholar 

  25. Hansen JM, Harris C. Redox control of teratogenesis. Reprod Toxicol. 2013;35:165–79.

    CAS  PubMed  Google Scholar 

  26. Harris C, Dixon M, Hansen JM. Glutathione depletion modulates methanol, formaldehyde and formate toxicity in cultured rat conceptuses. Cell Biol Toxicol. 2004;20:133–45.

    CAS  PubMed  Google Scholar 

  27. Hiranruengchok R, Harris C. Glutathione oxidation and embryotoxicity elicited by diamide in the developing rat conceptus in vitro. Toxicol Appl Pharmacol. 1993;120:62–71.

    CAS  PubMed  Google Scholar 

  28. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C – dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes. 2000;49:1939–45.

    CAS  PubMed  Google Scholar 

  29. Janssen-Heininger YMW, Mossman BT, Heintz NH, Forman HJ, Kalyanaraman B, Finkel T, Stamler JS, Rhee SG, van der Vliet A. Redox-based regulation of signal transduction: principles, pitfalls, and promises. Free Radic Biol Med. 2008;45:1–17.

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Jeng W, Ramkissoon A, Parman T, Wells PG. Prostaglandin H synthase-catalyzed bioactivation of amphetamines to free radical intermediates that cause CNS regional DNA oxidation and nerve terminal degeneration. FASEB J. 2006;20:638–50.

    CAS  PubMed  Google Scholar 

  31. Jovanovic SV, Simic MG. One-electron redox potentials of purines and pyrimidines. J Phys Chem. 1986;90:974–8.

    CAS  Google Scholar 

  32. Kadiiska MB, Mason RP. Acute methanol intoxication generates free radicals in rats: an ESR spin trapping investigation. Free Radic Biol Med. 2000;28:1106–14.

    CAS  PubMed  Google Scholar 

  33. Kasapinovic S, McCallum GP, Wiley MJ, Wells PG. The peroxynitrite pathway in development: phenytoin and benzo[a]pyrene embryopathies in inducible nitric oxide synthase (iNOS) knockout mice. Free Radic Biol Med. 2004;37:1703–11.

    CAS  PubMed  Google Scholar 

  34. Kennedy JC, Memet S, Wells PG. Antisense evidence for nuclear factor kB-dependent embryopathies initiated by phenytoin-enhanced oxidative stress. Mol Pharmacol. 2004;66:404–12.

    CAS  PubMed  Google Scholar 

  35. Khobta A, Anderhub S, Kitsera N, Epe B. Gene silencing induced by oxidative DNA base damage: association with local decrease of histone H4 acetylation in the promoter region. Nucleic Acids Res. 2010;38:4285–95.

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Kim PM, Wells PG. Phenytoin-initiated hydroxyl radical formation: characterization by enhanced salicylate hydroxylation. Mol Pharmacol. 1996;49:172–81.

    CAS  PubMed  Google Scholar 

  37. Kitsera N, Stathis D, Luhnsdorf B, Muller H, Carell T, Epe B, Khobta A. 8-Oxo-7,8-dihydroguanine in DNA does not constitute a barrier to transcription, but is converted into transcription-blocking damage by OGG1. Nucleic Acids Res. 2011;39:5926–34.

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Klungland A, Bjelland S. Oxidative damage to purines in DNA: role of mammalian Ogg1. DNA Repair. 2007;6:481–8.

    CAS  PubMed  Google Scholar 

  39. Klungland A, Rosewell I, Hollenbach S, Larsen E, Daly G, Epe B, Seeberg E, Lindahl T, Barnes DE. Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage. Proc Natl Acad Sci U S A. 1999;96:13300–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Knecht KT, Bradford BU, Mason RP, Thurman RG. In vivo formation of a free radical metabolite of ethanol. Mol Pharmacol. 1990;38:26–30.

    CAS  PubMed  Google Scholar 

  41. Knobloch J, Reimann K, Klotz LO, Ruther U. Thalidomide resistance is based on the capacity of the glutathione-dependent antioxidant defense. Mol Pharm. 2008;5:1138–44.

    CAS  PubMed  Google Scholar 

  42. Kotch LE, Chen SY, Sulik KK. Ethanol-induced teratogenesis: free radical damage as a possible mechanism. Teratology. 1995;52:128–36.

    CAS  PubMed  Google Scholar 

  43. Kubow S, Wells PG. In vitro bioactivation of phenytoin to a reactive free radical intermediate by prostaglandin synthetase, horseradish peroxidase, and thyroid peroxidase. Mol Pharmacol. 1989;35:504–11.

    CAS  PubMed  Google Scholar 

  44. Kwon J, Lee S-R, Yang K-S, Ahn Y, Kim YJ, Stadtman ER, Rhee SG. Reversible oxidation and inactivation of the tumor suppressor PTEN in cells stimulated with peptide growth factors. Proc Natl Acad Sci U S A. 2004;101:16419–24.

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Laposa RR, Henderson JT, Xu E, Wells PG. Atm-null mice exhibit enhanced radiation-induced birth defects and a hybrid form of embryonic cell death indicating a teratological suppressor function for ATM. FASEB J. 2004;18:896–8.

    CAS  PubMed  Google Scholar 

  46. Le Belle JE, Orozco NM, Paucar AA, Saxe JP, Mottahedeh J, Pyle AD, Wu H, Kornblum HI. Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner. Cell Stem Cell. 2011;8:59–71.

    PubMed Central  PubMed  Google Scholar 

  47. Lee CJJ, Goncalves LL, Wells PG. Embryopathic effects of thalidomide and its hydrolysis products in rabbit embryo culture: evidence for a prostaglandin H synthase (PHS)-dependent, reactive oxygen species (ROS)-mediated mechanism. FASEB J. 2011;25:2468–83.

    CAS  PubMed  Google Scholar 

  48. Lee RD, An SM, Kim SS, Rhee GS, Kwack SJ, Seok JH, Chae SY, Park CH, Choi YW, Kim HS, Cho HY, Lee BM, Park KL. Neurotoxic effects of alcohol and acetaldehyde during embryonic development. J Toxicol Environ Health. 2005;68:2147–62.

    Google Scholar 

  49. Liu L, Wells PG. In vivo phenytoin-initiated oxidative damage to proteins and lipids in murine maternal hepatic and embryonic tissue organelles: potential molecular targets of chemical teratogenesis. Toxicol Appl Pharmacol. 1994;125:247–55.

    CAS  PubMed  Google Scholar 

  50. Maruyama A, Kusama T. Measurement of DNA damage in ICR mouse embryos at preimplantation stage using a comet assay. Congenit Anom. 1998;38:375–83.

    CAS  Google Scholar 

  51. McCallum GP, Wong AW, Wells PG. Cockayne syndrome B (CSB) protects against methamphetamine-enhanced oxidative DNA damage in murine fetal brain and postnatal neurodevelopmental deficits. Antioxid Redox Signal. 2011;14:747–56.

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Mellén M, Ayata P, Dewell S, Kriaucionis S, Heintz N. MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell. 2012;151: 1417–30.

    PubMed Central  PubMed  Google Scholar 

  53. Miller L, Pinto D, Wells PG. Embryonic DNA repair and ethanol-initiated behavioural deficits in oxoguanine glycosylase 1 (OGG1) knockout mice: a role for oxidatively damaged DNA and protection by a free radical spin trapping agent. Toxicol Sci: (Supplement: The Toxicologist) 2013;132(131):218 (Abstract No. 1022).

    Google Scholar 

  54. Miller L, Pinto DJ, Wells PG. Oxidative DNA damage in the in utero initiation of postnatal neurodevelopmental deficits by normal fetal and ethanol-enhanced oxidative stress in oxoguanine glycosylase 1 (ogg1) knockout mice (2014); (submitted).

    Google Scholar 

  55. Miller L, Shapiro AM, Cheng J, Wells PG. The free radical spin trapping agent phenylbutylnitrone reduces fetal brain DNA oxidation and postnatal cognitive deficits caused by in utero exposure to a non-structurally teratogenic dose of ethanol: a role for oxidative stress. Free Radic Biol Med. 2013;60:223–32.

    CAS  PubMed  Google Scholar 

  56. Miller L, Shapiro AM, Wells PG. Embryonic catalase protects against ethanol-initiated DNA oxidation and teratogenesis in acatalasemic and human catalase-expressing mice. Toxicol Sci. 2013;134:400–11.

    Google Scholar 

  57. Miller L, Wells PG. Altered methanol embryopathies in embryo culture with mutant catalase-deficient mice and transgenic mice expressing human catalase. Toxicol Appl Pharmacol. 2011;252:55–61.

    CAS  PubMed  Google Scholar 

  58. Miranda AF, Wiley MJ, Wells PG. Evidence for embryonic peroxidase-catalyzed bioactivation and glutathione-dependent cytoprotection in phenytoin teratogenicity: modulation by eicosatetraynoic acid and buthionine sulfoximine in murine embryo culture. Toxicol Appl Pharmacol. 1994;124:230–41.

    CAS  PubMed  Google Scholar 

  59. Moallem SA, Hales BF. The role of p53 and cell death by apoptosis and necrosis in 4-hydroperoxycyclophosphamide-induced limb malformations. Development. 1998;125: 3225–34.

    CAS  PubMed  Google Scholar 

  60. Montoliu C, Sancho-Tello M, Azorin I, Burgal M, Valles S, Renau-Piqueras J, Guerri C. Ethanol increases cytochrome P4502E1 and induces oxidative stress in astrocytes. J Neurochem. 1995;65:2561–70.

    CAS  PubMed  Google Scholar 

  61. Moore K, Persaud TVN. The developing human: clinically oriented embryology. 8th ed. Philadelphia: W.B. Saunders; 2007.

    Google Scholar 

  62. Naya M, Mataki Y, Takahira H, Deguchi T, Yasuda M. Effects of phorone and/or buthionine sulfoximine on teratogenicity of 5-fluorouracil in mice. Teratology. 1990;41:275–80.

    CAS  PubMed  Google Scholar 

  63. Naya M, Yasuda M. Effects of glutathione and related compounds on teratogenicity of 5-fluorouracil or cadmium hydrochloride in mice*. Congenit Anom. 1997;37:337–44.

    CAS  Google Scholar 

  64. Nayanatara AK, Nagaraja HS, Ramaswamy C, Bhagyalakshmi K, Ramesh Bhat M, Harini N. Estimation of tissue lipid peroxidation level and organ weight in litters of wistar rats exposed to prenatal alcohol ingestion. J Physiol Biomed Sci. 2009;22:44–7.

    Google Scholar 

  65. Neubert D, Barrach HJ, Merker HJ. Drug-induced damage in the embryo or fetus. New York: Springer; 1980.

    Google Scholar 

  66. Nicol CJ, Harrison ML, Laposa RR, Gimelshtein IL, Wells PG. A teratologic suppressor role for p53 in benzo[a]pyrene-treated transgenic p53-deficient mice. Nat Genet. 1995;10: 181–7.

    CAS  PubMed  Google Scholar 

  67. Nicol CJ, Zielenski J, Tsui L-C, Wells PG. An embryoprotective role for glucose-6-phosphate dehydrogenase in developmental oxidative stress and chemical teratogenesis. FASEB J. 2000;14:111–27.

    CAS  PubMed  Google Scholar 

  68. Nonn L, Williams RR, Erickson RP, Powis G. The absence of mitochondrial thioredoxin 2 causes massive apoptosis, exencephaly, and early embryonic lethality in homozygous mice. Mol Cell Biol. 2003;23:916–22.

    CAS  PubMed Central  PubMed  Google Scholar 

  69. Norimura T, Nomoto S, Katsuki M, Gondo Y, Kondo S. p53-dependent apoptosis suppresses radiation-induced teratogenesis. Nat Med. 1996;2:577–80.

    CAS  PubMed  Google Scholar 

  70. Ondovcik SL, Tamblyn L, McPherson JP, Wells PG. Oxoguanine glycosylase 1 (OGG1) protects cells from DNA double-strand break damage following methylmercury exposure. Toxicol Sci. 2012;128:272–83.

    CAS  PubMed  Google Scholar 

  71. Ondovcik SL, Tamblyn L, McPherson JP, Wells PG. Sensitivity to methylmercury toxicity is enhanced in oxoguanine glycosylase 1 knockout murine embryonic fibroblasts and is dependent on cellular proliferation capacity. Toxicol Appl Pharmacol. 2013;270:23–30.

    CAS  PubMed  Google Scholar 

  72. Ozolins TR, Siksay DL, Wells PG. Modulation of embryonic glutathione peroxidase activity and phenytoin teratogenicity by dietary deprivation of selenium in CD-1 mice. J Pharmacol Exp Ther. 1996;277:945–53.

    CAS  PubMed  Google Scholar 

  73. Parman T, Chen G, Wells PG. Free radical intermediates of phenytoin and related teratogens. Prostaglandin H synthase-catalyzed bioactivation, electron paramagnetic resonance spectrometry, and photochemical product analysis. J Biol Chem. 1998;273:25079–88.

    CAS  PubMed  Google Scholar 

  74. Parman T, Wells PG. Embryonic prostaglandin H synthase-2 (PHS-2) expression and benzo[a]pyrene teratogenicity in PHS-2 knockout mice. FASEB J. 2002;16:1001–9.

    CAS  PubMed  Google Scholar 

  75. Parman T, Wiley MJ, Wells PG. Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity. Nat Med. 1999;5:582–5.

    CAS  PubMed  Google Scholar 

  76. Pastoriza-Gallego M, Armier J, Sarasin A. Transcription through 8-oxoguanine in DNA repair-proficient and Csb(−)/Ogg1(−) DNA repair-deficient mouse embryonic fibroblasts is dependent upon promoter strength and sequence context. Mutagenesis. 2007;22:343–51.

    CAS  PubMed  Google Scholar 

  77. Perera F, Herbstman J. Prenatal environmental exposures, epigenetics, and disease. Reprod Toxicol. 2011;31:363–73.

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Planchon SM, Waite KA, Eng C. The nuclear affairs of PTEN. J Cell Sci. 2008;121: 249–53.

    CAS  PubMed  Google Scholar 

  79. Preston TJ, Henderson JT, McCallum GP, Wells PG. Base excision repair of reactive oxygen species-initiated 7,8-dihydro-8-oxo-2′-deoxyguanosine inhibits the cytotoxicity of platinum anticancer drugs. Mol Cancer Ther. 2009;8:2015–26.

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Preston TJ, Henderson JT, McCallum GP, Wells PG. Base excision repair of reactive oxygen species-initiated 7,8-dihydro-8-oxo-2′-deoxyguanosine inhibits the cytotoxicity of platinum anticancer drugs. Mol Cancer Ther. 2010;8:2015–26.

    Google Scholar 

  81. Ramkissoon A, Wells PG. Developmental role of nuclear factor-E2-related factor 2 (Nrf2) in protecting against methamphetamine fetal toxicity and postnatal neurodevelopmental deficits. Free Radic Biol Med. 2013;65:620–31.

    Google Scholar 

  82. Roy D, Liehr JG. Estrogen, DNA damage and mutations. Mutat Res. 1999;424:107–15.

    CAS  PubMed  Google Scholar 

  83. Rutledge JC. Developmental toxicity induced during early stages of mammalian embryogenesis. Mutat Res. 1997;396:113–27.

    CAS  PubMed  Google Scholar 

  84. Sakamaki H, Akazawa S, Ishibashi M, Izumino K, Takino H, Yamasaki H, Yamaguchi Y, Goto S, Urata Y, Kondo T, Nagataki S. Significance of glutathione-dependent antioxidant system in diabetes-induced embryonic malformations. Diabetes. 1999;48:1138–44.

    CAS  PubMed  Google Scholar 

  85. Schlisser AE, Yan J, Hales BF. Teratogen-induced oxidative stress targets glyceraldehyde-3-phosphate dehydrogenase in the organogenesis stage mouse embryo. Toxicol Sci. 2010;118: 686–95.

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Schwab JG, Pena L, Waggoner D, Pytel P. Two Children with macrocephaly, developmental delay, and PTEN mutation. Clin Pediatr (Phila). 2009;48:89–92.

    Google Scholar 

  87. Sha K, Winn LM. Characterization of valproic acid-initiated homologous recombination. Birth Defects Res B Dev Reprod Toxicol. 2010;89:124–32.

    CAS  PubMed  Google Scholar 

  88. Shapiro AM, Miller L, Wells PG. Breast cancer 1 (BRCA1)-deficient mice develop normally but are more susceptible to ethanol- and methamphetamine-initiated embryopathies (Abstract). Toxicol Sci (supplement: The Toxicologist) 2013;132:213.

    Google Scholar 

  89. Shivananjappa MM, Muralidhara. Differential oxidative stress induction and lethality of rat embryos after maternal exposure to t-butyl hydroperoxide during postimplantation period. Drug Chem Toxicol. 2013;36:209–16.

    CAS  PubMed  Google Scholar 

  90. Siu M, Wiley MJ, Wells PG. Methanol teratogenicity in mutant mice with deficient catalase activity and transgenic mice expressing human catalase. Reprod Toxicol. 2013;36:33–9.

    CAS  PubMed  Google Scholar 

  91. Skrzydlewska E, Elas M, Farbiszewski R, Roszkowska A. Effect of methanol intoxication on free-radical induced protein oxidation. J Appl Toxicol. 2000;20:239–43.

    CAS  PubMed  Google Scholar 

  92. Skrzydlewska E, Farbiszewski R. Liver and serum antioxidant status after methanol intoxication in rats. Acta Biochim Pol. 1997;44:139–45.

    CAS  PubMed  Google Scholar 

  93. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324:930–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Tung EWY, Winn LM. Valproic acid increases formation of reactive oxygen species and induces apoptosis in postimplantation embryos: a role for oxidative stress in valproic acid-induced neural tube defects. Mol Pharmacol. 2011;80:979–87.

    CAS  PubMed  Google Scholar 

  95. Valinluck V, Tsai H-H, Rogstad DK, Burdzy A, Bird A, Sowers LC. Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res. 2004;32:4100–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Wells PG, Bhuller Y, Chen CS, Jeng W, Kasapinovic S, Kennedy JC, Kim PM, Laposa RR, McCallum GP, Nicol CJ, Parman T, Wiley MJ, Wong AW. Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species. Toxicol Appl Pharmacol. 2005;207:354–66.

    PubMed  Google Scholar 

  97. Wells PG, Kim PM, Laposa RR, Nicol CJ, Parmana T, Winn LM. Oxidative damage in chemical teratogenesis. Mutat Res. 1997;396:65–78.

    CAS  PubMed  Google Scholar 

  98. Wells PG, Lee CJJ, McCallum GP, Perstin J, Harper PA. Receptor- and reactive intermediate-mediated mechanisms of teratogenesis. In: Adverse Drug Reactions, Uetrecht JP, editor. Heidelberg: Springer; 2009. p. 131–62.

    Google Scholar 

  99. Wells PG, McCallum GP, Chen CS, Henderson JT, Lee CJ, Perstin J, Preston TJ, Wiley MJ, Wong AW. Oxidative stress in developmental origins of disease: teratogenesis, neurodevelopmental deficits, and cancer. Toxicol Sci. 2009;108:4–18.

    CAS  PubMed  Google Scholar 

  100. Wells PG, McCallum GP, Miller L, Siu M, Sweeting JN. Oxidative stress and species differences in the metabolism, developmental toxicity and carcinogenic potential of methanol and ethanol. In: The Toxicology of Methanol, Clary JJ, editor. Hoboken: Wiley; 2013. p. 169–253.

    Google Scholar 

  101. Wells PG, Zubovits JT, Wong ST, Molinari LM, Ali S. Modulation of phenytoin teratogenicity and embryonic covalent binding by acetylsalicylic acid, caffeic acid, and alpha-phenyl-N-t-butylnitrone: implications for bioactivation by prostaglandin synthetase. Toxicol Appl Pharmacol. 1989;97:192–202.

    CAS  PubMed  Google Scholar 

  102. Wentzel P, Eriksson UJ. Ethanol-induced fetal dysmorphogenesis in the mouse is diminished by high antioxidative capacity of the mother. Toxicol Sci. 2006;92:416–22.

    CAS  PubMed  Google Scholar 

  103. Wentzel P, Rydberg U, Eriksson UJ. Antioxidative treatment diminishes ethanol-induced congenital malformations in the rat. Alcohol Clin Exp Res. 2006;30:1752–60.

    CAS  PubMed  Google Scholar 

  104. Wilson JG. Experimental studies on congenital malformations. J Chronic Dis. 1959;10: 111–30.

    CAS  PubMed  Google Scholar 

  105. Winn LM, Wells PG. Evidence for embryonic prostaglandin H synthase-catalyzed bioactivation and reactive oxygen species-mediated oxidation of cellular macromolecules in phenytoin and benzo[a]pyrene teratogenesis. Free Radic Biol Med. 1997;22:607–21.

    CAS  PubMed  Google Scholar 

  106. Winn LM, Wells PG. Maternal administration of superoxide dismutase and catalase in phenytoin teratogenicity. Free Radic Biol Med. 1999;26:266–74.

    CAS  PubMed  Google Scholar 

  107. Winn LM, Wells PG. Evidence for Ras-dependent signal transduction in phenytoin teratogenicity. Toxicol Appl Pharmacol. 2002;184:144–52.

    CAS  PubMed  Google Scholar 

  108. Wong AW, McCallum GP, Jeng W, Wells PG. Oxoguanine glycosylase 1 protects against methamphetamine-enhanced fetal brain oxidative DNA damage and neurodevelopmental deficits. J Neurosci. 2008;28:9047–54.

    CAS  PubMed  Google Scholar 

  109. Wong M, Helston LM, Wells PG. Enhancement of murine phenytoin teratogenicity by the gamma-glutamylcysteine synthetase inhibitor L-buthionine-(S, R)-sulfoximine and by the glutathione depletor diethyl maleate. Teratology. 1989;40:127–41.

    CAS  PubMed  Google Scholar 

  110. Wong M, Wells PG. Effects of N-acetylcysteine on fetal development and on phenytoin teratogenicity in mice. Teratog Carcinog Mutagen. 1988;8:65–79.

    CAS  PubMed  Google Scholar 

  111. Wong M, Wells PG. Modulation of embryonic glutathione reductase and phenytoin teratogenicity by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). J Pharmacol Exp Ther. 1989;250: 336–42.

    CAS  PubMed  Google Scholar 

  112. Wubah JA, Ibrahim MM, Gao X, Nguyen D, Pisano MM, Knudsen TB. Teratogen-induced eye defects mediated by p53-dependent apoptosis. Curr Biol. 1996;6:60–9.

    CAS  PubMed  Google Scholar 

  113. Xu DX, Chen YH, Zhao L, Wang H, Wei W. Reactive oxygen species are involved in lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation in mice. Am J Obstet Gynecol. 2006;195:1707–14.

    CAS  PubMed  Google Scholar 

  114. Yu T, Jhun BS, Yoon Y. High-glucose stimulation increases reactive oxygen species production through the calcium and mitogen-activated protein kinase-mediated activation of mitochondrial fission. Antioxid Redox Signal. 2011;14:425–37.

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Yu WK, Wells PG. Evidence for lipoxygenase-catalyzed bioactivation of phenytoin to a teratogenic reactive intermediate: in vitro studies using linoleic acid-dependent soybean lipoxygenase, and in vivo studies using pregnant CD-1 mice. Toxicol Appl Pharmacol. 1995;131:1–12.

    CAS  PubMed  Google Scholar 

  116. Zabihi S, Loeken MR. Understanding diabetic teratogenesis: where are we now and where are we going? Birth Defects Res A Clin Mol Teratol. 2010;88:779–90.

    CAS  PubMed  Google Scholar 

  117. Zhao L, Chen YH, Wang H, Ji YL, Ning H, Wang SF, Zhang C, Lu JW, Duan ZH, Xu DX. Reactive oxygen species contribute to lipopolysaccharide-induced teratogenesis in mice. Toxicol Sci. 2008;103:149–57.

    CAS  PubMed  Google Scholar 

  118. Zhou J, Blundell J, Ogawa S, Kwon CH, Zhang W, Sinton C, Powell CM, Parada LF. Pharmacological inhibition of mTORC1 suppresses anatomical, cellular, and behavioral abnormalities in neural-specific Pten knock-out mice. J Neurosci. 2009;29:1773–83.

    CAS  PubMed Central  PubMed  Google Scholar 

  119. Wells, P. G., McCallum, G. P., Lam, K. C. H., Henderson, J. T. and Ondovcik, S. L. (2010). Oxidative DNA damage and repair in teratogenesis and neurodevelopmental deficits. Birth Defects Research Part C: Embryo Today: Reviews 90, 103–109.

    Google Scholar 

  120. Liu, Y., Balaraman, Y., Wang, G., Nephew, K. P. and Zhou, F. C. (2009). Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation. Epigenetics 4, 500–511.

    Google Scholar 

  121. Perkins, A., Lehmann, C., Lawrence, R. C. and Kelly, S. J. (2013). Alcohol exposure during development: Impact on the epigenome. International Journal of Developmental Neuroscience 31, 391–397.

    Google Scholar 

  122. Zimmerman EF, Potturi RB, Resnick E, Fisher JE. Role of oxygen free radicals in cocaine-induced vascular disruption in mice. Teratology. 1994;49:192–201.

    CAS  PubMed  Google Scholar 

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Acknowledgment

Research from the authors’ laboratory was supported by grants from the Canadian Institutes of Health Research (CIHR). AMS was supported in part by a CIHR Frederick Banting and Charles Best Canada Graduate Scholarship.

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    Authors and Affiliations

    1. Division of Biomolecular Sciences, Faculty of Pharmacy, and Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

      Peter G. Wells Pharm.D.

    2. Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada

      Lutfiya Miller-Pinsler

    3. Division of Biomolecular Sciences, Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada

      Aaron M. Shapiro

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    1. Peter G. Wells Pharm.D.
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    2. Lutfiya Miller-Pinsler
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    3. Aaron M. Shapiro
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    Correspondence to Peter G. Wells Pharm.D. .

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    Editors and Affiliations

    1. University of Penn, Perelman Sch of Med Professor of Pediatrics, Children's Hospital of Philadelphia Division of Neonatology, Philadelphia, Pennsylvania, USA

      Phyllis A. Dennery

    2. Lab of Oxidative Stress Policlinico “Le Scotte“, University of Siena Dept of Peds, Obstetrics & Reprod Med, Siena, Italy

      Giuseppe Buonocore

    3. Department of Pediatrics, University of Oslo Faculty of Medicine Rikshospitalit Medical Center, Oslo, Norway

      Ola Didrik Saugstad

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    Wells, P.G., Miller-Pinsler, L., Shapiro, A.M. (2014). Impact of Oxidative Stress on Development. In: Dennery, P., Buonocore, G., Saugstad, O. (eds) Perinatal and Prenatal Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1405-0_1

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