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Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes

Abstract

Purpose

Preeclampsia is known to be a leading cause of mortality and morbidity among mothers and their infants. Approximately 3–8% of all pregnancies in the US are complicated by preeclampsia and another 5–7% by hypertensive symptoms. However, less is known about its long-term influence on infant neurobehavioral development. The current review attempts to demonstrate new evidence for imprinting gene dysregulation caused by hypertension, which may explain the link between maternal preeclampsia and neurocognitive dysregulation in offspring.

Method

Pub Med and Web of Science databases were searched using the terms “preeclampsia,” “gestational hypertension,” “imprinting genes,” “imprinting dysregulation,” and “epigenetic modification,” in order to review the evidence demonstrating associations between preeclampsia and suboptimal child neurodevelopment, and suggest dysregulation of placental genomic imprinting as a potential underlying mechanism.

Results

The high mortality and morbidity among mothers and fetuses due to preeclampsia is well known, but there is little research on the long-term biological consequences of preeclampsia and resulting hypoxia on the fetal/child neurodevelopment. In the past decade, accumulating evidence from studies that transcend disciplinary boundaries have begun to show that imprinted genes expressed in the placenta might hold clues for a link between preeclampsia and impaired cognitive neurodevelopment. A sudden onset of maternal hypertension detected by the placenta may result in misguided biological programming of the fetus via changes in the epigenome, resulting in suboptimal infant development.

Conclusion

Furthering our understanding of the molecular and cellular mechanisms through which neurodevelopmental trajectories of the fetus/infant are affected by preeclampsia and hypertension will represent an important first step toward preventing adverse neurodevelopment in infants.

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Fig. 1

Adapted from Lambertini et al. [66]; Perera and Herbstman [69]

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References

  1. 1.

    McCalla CO, Nacharaju VL, Muneyyirci-Delale O, Glasgow S, Feldman JG (1998) Placental 11β-hydroxysteroid dehydrogenase activity in normotensive and pre-eclamptic pregnancies. Steroids 63:511–515

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Williams MA, Miller RS, Qiu C, Cripe SM, Gelaye B, Enquobahrie D (2010) Associations of early pregnancy sleep duration with trimester-specific blood pressures and hypertensive disorders in pregnancy. Sleep 33:1363–1371

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Osterman, MJ, Martin JA, Mathews TJ, Hamilton BE (2011) Expanded data from the new birth certificate, 2008. National vital statistics reports: from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System 59:1–28

  4. 4.

    Podymow T, August P (2007) Hypertension in pregnancy. Adv Chronic Kidney Dis 14:178–190

    Article  PubMed  Google Scholar 

  5. 5.

    Chang J, Elam-Evans LD, Berg CJ, Herndon J, Flowers L, Seed KA, Syverson CJ (2003) Pregnancy-related mortality surveillance–united states, 1991–1999. Morbidity and mortality weekly report. Surveill Summ 52:1–8

    Google Scholar 

  6. 6.

    Saadat M, Nejad SM, Habibi G, Sheikhvatan M (2007) Maternal and neonatal outcomes in women with preeclampsia. Taiwan J Obstetr Gynecol 46:255–259

    Article  Google Scholar 

  7. 7.

    Getahun, D, Rhoads, GG, Demissie, K, Lu, SE, Quinn, VP, Fassett, MJ, Wing, DA, Jacobsen, SJ (2012) In utero exposure to ischemic-hypoxic conditions and attention-deficit/hyperactivity disorder. Pediatrics 131:e53–e61

    Article  PubMed  Google Scholar 

  8. 8.

    Mann JR, McDermott S (2010) Are maternal genitourinary infection and pre-eclampsia associated with adhd in school-aged children? J Atten Disord 15:667–673

    Article  PubMed  Google Scholar 

  9. 9.

    Silva D, Colvin L, Hagemann E, Bower C (2013) Environmental risk factors by gender associated with attention-deficit/hyperactivity disorder. Pediatrics 133:e14–e22

    Article  PubMed  Google Scholar 

  10. 10.

    Whitehouse, AJO, Robinson M, Newnham, JP P en nell CE (2012) Do hypertensive diseases of pregnancy disrupt neurocognitive development in offspring? Paediatr Perinat Epidemiol 26:101–108

    Article  PubMed  Google Scholar 

  11. 11.

    Nomura Y, Marks DJ, Grossman B, Yoon M, Loudon H, Stone J, Halperin JM (2012) Exposure to gestational diabetes mellitus and low socioeconomic status. Arch Pediatr Adolesc Med 166:337

    Article  PubMed  Google Scholar 

  12. 12.

    Ornoy, A, Ratzon, N, Greenbaum, C, Wolf, A, Dulitzky, M (2001) School-age children born to diabetic mothers and to mothers with gestational diabetes exhibit a high rate of inattention and fine and gross motor impairment. J Pediatr Endocrinol Metabol 14:681–690

    Article  Google Scholar 

  13. 13.

    Bressan FF, De Bem, THC, Perecin F, Lopes FL, Ambrosio CE, Meirelles FV, Miglino MA (2009) Unearthing the roles of imprinted genes in the placenta. Placenta 30:823–834

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Davies W, Isles AR, Wilkinson LS (2005) Imprinted gene expression in the brain. Neurosci Biobehav Rev 29:421–430

  15. 15.

    Roseboom T, de Rooij S, Painter R (2006) The dutch famine and its long-term consequences for adult health. Early Hum Dev 82:485–491

    Article  PubMed  Google Scholar 

  16. 16.

    Susser E, Hoek HW, Brown A (1998) Neurodevelopmental disorders after prenatal famine: the story of the dutch famine study. Am J Epidemiol 147:213–216

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Rasmussen S, Irgens LM (2003) Fetal growth and body proportion in preeclampsia. Obstet Gynecol 101:575–583

    PubMed  Google Scholar 

  18. 18.

    Henriksen T, Clausen T (2002) The fetal origins hypothesis: placental insufficiency and inheritance versus maternal malnutrition in well-nourished populations. Acta Obstet Gynecol Scand 81(2):112–114

    Article  PubMed  Google Scholar 

  19. 19.

    Wu G, Imhoff-Kunsch B, Girard AW (2012) Biological mechanisms for nutritional regulation of maternal health and fetal development. Paediatr Perinat Epidemiol 26(Suppl 1):4–26. doi:10.1111/j.1365-3016.2012.01291.x

    Article  PubMed  Google Scholar 

  20. 20.

    Bramham K, Briley AL, Seed P, Poston L, Shennan AH, Chappell LC (2011) Adverse maternal and perinatal outcomes in women with previous preeclampsia: A prospective study. Am J Obstet Gynecol 204(512):e1-12.e9

    Google Scholar 

  21. 21.

    Habli M, Levine RJ, Qian C, Sibai B (2007) Neonatal outcomes in pregnancies with preeclampsia or gestational hypertension and in normotensive pregnancies that delivered at 35, 36, or 37 weeks of gestation. Am J Obstet Gynecol 197(406):e1-06.e7

    Google Scholar 

  22. 22.

    Jelin AC, Cheng YW, Shaffer BL, Kaimal AJ, Little SE, Caughey AB (2010) Early-onset preeclampsia and neonatal outcomes. J Matern-Fetal Neonat Med 23:389–392

    Article  Google Scholar 

  23. 23.

    Liggins GC, Howie RN (1972) A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 50:515–525

    CAS  PubMed  Google Scholar 

  24. 24.

    Ødegard RA, Vatten LJ, Nilsen ST, Salvesen KÅ, Austgulen R (2000) Preeclampsia and fetal growth. Obstetr Gynecol 96:950–955

    Google Scholar 

  25. 25.

    Swank, M, Nageotte, M, Hatfield, T (2012) Necrotizing pancreatitis associated with severe preeclampsia. Obstetr Gynecol 120:453–455

    Article  Google Scholar 

  26. 26.

    Benediktsson R, Lindsay RS, Noble J, Seckl JR, Edwards, CRW (1993) Glucocorticoid exposure in utero: New model for adult hypertension. Lancet 341:339–341

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Edwards, CRW, Benediktsson R, Lindsay RS, Seckl JR (1993) Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension? Lancet 341:355–357

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Kalder, M, Ulrich S, Hitschold T, Berle P (1995) [fetal development in mild and severe pre-eclampsia: Correlation with maternal laboratory parameters and doppler ultrasound]. Zeitschrift fur Geburtshilfe und Neonatologie 199:13–17

    CAS  PubMed  Google Scholar 

  29. 29.

    Liu C-M, Cheng P-J, Chang S-D (2008) Maternal complications and perinatal outcomes associated with gestational hypertension and severe preeclampsia in taiwanese women. Taiwan yi zhi=J Formos Med Assoc 107:129–138

    Article  Google Scholar 

  30. 30.

    Leuner B, Gould E (2010) Structural plasticity and hippocampal function. Annu Rev Psychol 61:111–140

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Jones BP, Bell EA, Maroof M (1999) Epidural labor analgesia in parturient with von willebrandʼs disease type iia and severe preeclampsia. Anesthesiology 90:1219–1220

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Masoura S, Kalogiannidis I, Margioula-Siarkou C, Diamanti E, Papouli M, Drossou-Agakidou V, Prapas N, Agorastos T (2012) Neonatal outcomes of late preterm deliveries with pre-eclampsia. Minerva Ginecol 64:109–115

    CAS  PubMed  Google Scholar 

  33. 33.

    Nomura Y, Lambertini L, Rialdi A, Lee M, Mystal EY, Grabie M, Manaster I, Huynh N, Finik J et al (2013) Global methylation in the placenta and umbilical cord blood from pregnancies with maternal gestational diabetes, preeclampsia, and obesity. Reprod Sci 21:131–137

    Article  PubMed  Google Scholar 

  34. 34.

    Bos AF, Einspieler C, Prechtl, HFR (2001) Intrauterine growth retardation, general movements, and neurodevelopmental outcome: a review. Dev Med Child Neurol 43:61

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Tolsa CB, Zimine S, Warfield SK, Freschi M, Rossignol AS, Lazeyras F, Hanquinet S, Pfizenmaier M, Hüppi PS (2004) Early alteration of structural and functional brain development in premature infants born with intrauterine growth restriction. Pediatr Res 56:132–138

    Article  PubMed  Google Scholar 

  36. 36.

    Arcangeli T, Thilaganathan B, Hooper R, Khan KS, Bhide A (2012) Neurodevelopmental delay in small babies at term: a systematic review. Ultrasound Obstet Gynecol 40(3):267–275. doi:10.1002/uog.11112

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Allin M, Matsumoto H, Santhouse AM, Nosarti C, AlAsady MHS, Stewart AL, Rifkin L, Murray RM (2001) Cognitive and motor function and the size of the cerebellum in adolescents born very pre-term. Brain 124:60–66

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Marlow N, Wolke D, Bracewell MA, Samara M (2005) Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med 352:9–19

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Moster D, Lie RT, Markestad T (2008) Long-term medical and social consequences of preterm birth. N Engl J Med 359:262–273

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Straub H, Adams M, Kim JJ, Silver RK (2012) Antenatal depressive symptoms increase the likelihood of preterm birth. Am J Obstet Gynecol 207(329):e1-29.e4

    Google Scholar 

  41. 41.

    Hack M, Schluchter M, Cartar L, Rahman M, Cuttler L, Borawski E (2003) Growth of very low birth weight infants to age 20 years. Pediatrics 112:e30–e38

    Article  PubMed  Google Scholar 

  42. 42.

    Mikkola K (2005) Neurodevelopmental outcome at 5 years of age of a national cohort of extremely low birth weight infants who were born in 1996–1997. Pediatrics 116:1391–1400

    Article  PubMed  Google Scholar 

  43. 43.

    Sung I-K, Vohr B, Oh W (1993) Growth and neurodevelopmental outcome of very low birth weight infants with intrauterine growth retardation: comparison with control subjects matched by birth weight and gestational age. J Pediatr 123:618–624

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Davis EP, Glynn LM, Schetter CD, Hobel C, Chicz-Demet AS, Man CA (2007) Prenatal exposure to maternal depression and cortisol influences infant temperament. J Am Acad Child Adolesc Psychiatry 46:737–746

    Article  PubMed  Google Scholar 

  45. 45.

    Huizink AC, Robles de Medina PG, Mulder EJH, Visser GHA, Buitelaar JK (2003) Stress during pregnancy is associated with developmental outcome in infancy. J Child Psychol Psychiat 44:810–818

    Article  PubMed  Google Scholar 

  46. 46.

    Marcus S, Lopez JF, McDonough S, MacKenzie MJ, Flynn H, Neal CR, Gahagan S, Volling B, Kaciroti N et al (2011) Depressive symptoms during pregnancy: Impact on neuroendocrine and neonatal outcomes. Infant Behav Dev 34:26–34

    Article  PubMed  Google Scholar 

  47. 47.

    Many A, Fattal A, Leitner Y, Kupferminc MJ, Harel S, Jaffa A (2003) Neurodevelopmental and cognitive assessment of children born growth restricted to mothers with and without preeclampsia. Hypertens Pregnancy 22:25–29

    Article  PubMed  Google Scholar 

  48. 48.

    Cheng S-W, Chou H-C, Tsou K-I, Fang L-J, Tsao P-N (2004) Delivery before 32 weeks of gestation for maternal pre-eclampsia: neonatal outcome and 2-year developmental outcome. Early Hum Dev 76:39–46

    Article  PubMed  Google Scholar 

  49. 49.

    Bayley N (2006) Bayley scales of infant and toddler development, third edition. In: Assessment H. (ed), PsycTESTS Dataset. Psych. Corporation, San Antonio

  50. 50.

    Posner MI, Rothbart MK, Sheese BE, Voelker P (2014) Developing attention: behavioral and brain mechanisms. Adv Neurosci 2014:1–9

    Article  Google Scholar 

  51. 51.

    Dougherty LR, Klein DN, Olino TM, Dyson M, Rose S (2009) Increased waking salivary cortisol and depression risk in preschoolers: the role of maternal history of melancholic depression and early child temperament. J Child Psychol Psychiatry 50:1495–1503

    Article  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Madsen KS, Jernigan TL, Iversen P, Frokjaer VG, Mortensen EL, Knudsen GM, Baaré, WFC (2012) Cortisol awakening response and negative emotionality linked to asymmetry in major limbic fibre bundle architecture. Psychiatry Res: Neuroimaging 201:63–72

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Whittle S, Allen NB, Lubman DI, Yücel M (2006) The neurobiological basis of temperament: Towards a better understanding of psychopathology. Neurosci Biobehav Rev 30:511–525

    Article  PubMed  Google Scholar 

  54. 54.

    Putnam, SP, Gartstein, MA, Rothbart, MK (2006) Measurement of fine-grained aspects of toddler temperament: the early childhood behavior questionnaire. Infant Behav Dev 29:386–401

    Article  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 15(4):264–269

    Article  Google Scholar 

  56. 56.

    Walker CK, Krakowiak P, Baker A, Hansen RL, Ozonoff S, Hertz-Picciotto I (2015) Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay. JAMA Pediatr 169(2):154–162. doi:10.1001/jamapediatrics.2014.2645

  57. 57.

    Walker CK, Ashwood P, Hertz-Picciotto I (2015) Preeclampsia, placental insufficiency, autism, and antiphospholipid antibodies-reply. JAMA Pediatr 169(6):606–607. doi:10.1001/jamapediatrics.2015.0345

    Article  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Schroeder DI, Schmidt RJ, Crary-Dooley FK, Walker CK, Ozonoff S, Tancredi DJ, Hertz-Picciotto I, LaSalle JM (2016) Placental methylome analysis from a prospective autism study. Mol Autism 7:51. doi:10.1186/s13229-016-0114-8

    Article  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Boyle CA, Decoufle P, Yeargin-Allsopp M (1994) Prevalence and health impact of developmental disabilities in us children. Pediatrics 93:399–403

    CAS  PubMed  Google Scholar 

  60. 60.

    Pastor PN, Reuben CA (2002) Attention deficit disorder and learning disability: United states, 1997–98. Vital and health statistics, series 10, number 206, PsycEXTRA Dataset. American Psychological Association (APA)

  61. 61.

    Baio J (2012) Prevalence of autism spectrum disorders–autism and developmental disabilities monitoring network, 14 sites, united states, 2008. In: Prevention, C.f.D.C.a. (ed.) Morbidity and mortality weekly report. Surveillance summaries, pp. 1–19

  62. 62.

    Liu JH (2009) Endocrinology of pregnancy, creasy and resnik’s maternal-fetal medicine: principles and practice. Elsevier BV, pp. 111–124

  63. 63.

    Petraglia F, Coukos G, Volpe A, Genazzani AR, Vale W (1991) Involvement of placental neurohormones in human parturition. Ann NY Acad Sci 622:331–340

    CAS  Article  PubMed  Google Scholar 

  64. 64.

    Yen SS (1994) The placenta as the third brain. J Reprod Med 39:277–280

    CAS  PubMed  Google Scholar 

  65. 65.

    Lambertini L, Lee TL, Chan WY, Lee MJ, Diplas A, Wetmur J, Chen J (2011) Differential methylation of imprinted genes in growth-restricted placentas. Reprod Sci 18:1111–1117

    CAS  Article  PubMed  Google Scholar 

  66. 66.

    Lambertini L, Lee M-J, Marsit JC, Che J (2012) Genomic imprinting in human placenta. Recent Advances in Research on the Human Placenta. InTech

  67. 67.

    Reik W (2001) Epigenetic reprogramming in mammalian development. Science 293:1089–1093

    CAS  Article  PubMed  Google Scholar 

  68. 68.

    Santos F, Dean W (2004) Epigenetic reprogramming during early development in mammals. Reproduction 127:643–651

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    Perera F, Herbstman J (2011) Prenatal environmental exposures, epigenetics, and disease. Reprod Toxicol 31:363–373

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  70. 70.

    DUJ The genomic imprinting website. Shortitle The genomic imprinting website. http://www.geneimprint.com/site/what-is-imprinting

  71. 71.

    Garg P, Borel C, Sharp AJ (2012) Detection of parent-of-origin specific expression quantitative trait loci by cis-association analysis of gene expression in trios. PLoS One 7:e41695

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Charalambous M, da Rocha ST, Ferguson-Smith AC (2007) Genomic imprinting, growth control and the allocation of nutritional resources: consequences for postnatal life. Curr Opin Endocrinol Diabetes Obes 14:3–12

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Shaikh MG (2011) 2.4.1 hypothalamic dysfunction (hypothalamic syndromes), Oxford Textbook of Endocrinology and Diabetes. Oxford University Press (OUP)

  74. 74.

    John RM (2013) Epigenetic regulation of placental endocrine lineages and complications of pregnancy. Biochm Soc Trans 41:701–709

    CAS  Article  Google Scholar 

  75. 75.

    McMinn J, Wei M, Schupf N, Cusmai J, Johnson EB, Smith AC, Weksberg R, Thaker HM, Tycko B (2006) Unbalanced placental expression of imprinted genes in human intrauterine growth restriction. Placenta 27:540–549

    CAS  Article  PubMed  Google Scholar 

  76. 76.

    Tycko B, Morison IM (2002) Physiological functions of imprinted genes. J Cell Physiol 192:245–258

    CAS  Article  PubMed  Google Scholar 

  77. 77.

    Newman, JRS, Ghaemmaghami S, Ihmels J, Breslow DK, Noble M, DeRisi JL, Weissman JS (2006) Single-cell proteomic analysis of s. Cerevisiae reveals the architecture of biological noise. Nature 441:840–846

    CAS  Article  PubMed  Google Scholar 

  78. 78.

    Zaitoun I, Downs KM, Rosa GJM, Khatib H (2010) Upregulation of imprinted genes in mice: An insight into the intensity of gene expression and the evolution of genomic imprinting. Epigenetics 5:149–158

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Elowitz MB (2002) Stochastic gene expression in a single cell. Science 297:1183–1186

    CAS  Article  PubMed  Google Scholar 

  80. 80.

    Ozbudak EM, Thattai M, Kurtser I, Grossman AD, van Oudenaarden A (2002) Regulation of noise in the expression of a single gene. Nat Genet 31:69–73

    CAS  Article  PubMed  Google Scholar 

  81. 81.

    Blake WJ, KÆrn M, Cantor CR, Collins JJ (2003) Noise in eukaryotic gene expression. Nature 422:633–637

    CAS  Article  PubMed  Google Scholar 

  82. 82.

    Fraser HB, Hirsh AE, Giaever G, Kumm J, Eisen MB (2004) Noise minimization in eukaryotic gene expression. PLoS Biol 2:e137

    Article  PubMed  PubMed Central  Google Scholar 

  83. 83.

    Batada NN, Hurst LD (2007) Evolution of chromosome organization driven by selection for reduced gene expression noise. Nat Genet 39:945–949

    CAS  Article  PubMed  Google Scholar 

  84. 84.

    Guerrero-Bosagna C, Skinner MK (2012) Environmentally induced epigenetic transgenerational inheritance of phenotype and disease. Mol Cell Endocrinol 354:3–8

    CAS  Article  PubMed  Google Scholar 

  85. 85.

    Dilinoy DC, Weidman JR, Jirtle RL (2007) Epigenetic gene regulation: linking early developmental environment to adult disease. Reprod Toxicol 23:297–307

    Article  Google Scholar 

  86. 86.

    Jirtle RL, Skinner MK (2007) Environmental epigenomics and disease susceptibility. Nat Rev Genet 8:253–262

    CAS  Article  PubMed  Google Scholar 

  87. 87.

    Kappil M, Lambertini L, Chen J (2015) Environmental influences on genomic imprinting. Curr Environ Health Rep 2:155–162

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Lambertini L (2014) Genomic imprinting. Curr Opin Pediatr 26:237–242

    Article  PubMed  Google Scholar 

  89. 89.

    Lambertini L, Marsit CJ, Sharma P, Maccani M, Ma Y, Hu J, Chen J (2012) Imprinted gene expression in fetal growth and development. Placenta 33:480–486

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Chen J, Li Q, Rialdi, Mystal A, EY, Ly, Finik J, Davey J, Lambertini T, Nomura LY (2014) Influences of maternal stress during pregnancy on the epi/genome: comparison of placenta and umbilical cord blood. Depress Anxiety 3:1–6

    Google Scholar 

  91. 91.

    Diplas AI, Lambertini L, Lee M-J, Sperling R, Lee YL, Wetmur JG, Chen J (2009) Differential expression of imprinted genes in normal and iugr human placentas. Epigenetics 4:235–240

    CAS  Article  PubMed  Google Scholar 

  92. 92.

    Green BB, Kappil M, Lambertini L, Armstrong DA, Guerin DJ, Sharp AJ, Lester BM, Chen J, Marsit CJ (2015) Expression of imprinted genes in placenta is associated with infant neurobehavioral development. Epigenetics 10:834–841

    Article  PubMed  PubMed Central  Google Scholar 

  93. 93.

    Lambertini L, Diplas AI, Lee M-J, Sperling R, Chen J, Wetmur JG (2008) A sensitive functional assay reveals frequent loss of genomic imprinting in human placenta. Epigenetics 3:261–269

    Article  PubMed  PubMed Central  Google Scholar 

  94. 94.

    Lambertini L, Diplas AL, Wetmur J, Lee MJ, Chen J (2009) Evaluation of genomic imprinting employing the analysis of loss of imprinting (loi) at the rna level: preliminary results. Eur J Oncol 14:161–169

    Google Scholar 

  95. 95.

    Marsit CJ, Lambertini L, Maccani MA, Koestler DC, Houseman EA, Padbury JF, Lester BM, Chen J (2012) Placenta-imprinted gene expression association of infant neurobehavior. J Pediatr 160(854–60):e2

    Google Scholar 

  96. 96.

    Mathers JC (2007) Early nutrition: Impact on epigenetics, nutrigenomics—opportunities in Asia. S. Karger AG, pp. 42–48

  97. 97.

    Kawasaki K, Kondoh E, Chigusa Y, Ujita M, Murakami R, Mogami H, Brown JB, Okuno Y, Konishi I (2014) Reliable pre-eclampsia pathways based on multiple independent microarray data sets. Mol Hum Reprod 21:217–224

    Article  PubMed  Google Scholar 

  98. 98.

    Enquobahrie DA, Meller M, Rice K, Psaty BM, Siscovick DS, Williams MA (2008) Differential placental gene expression in preeclampsia. Am J Obstet Gynecol 199(566):e1-66.e11

    Google Scholar 

  99. 99.

    Unek G, Ozmen A, Mendilcioglu I, Simsek M, Korgun ET (2014) The expression of cell cycle related proteins pcna, ki67, p27 and p57 in normal and preeclamptic human placentas. Tissue Cell 46:198–205

    CAS  Article  PubMed  Google Scholar 

  100. 100.

    Bourque DK, Avila L, Peñaherrera M, von Dadelszen P, Robinson WP (2010) Decreased placental methylation at the h19/igf2 imprinting control region is associated with normotensive intrauterine growth restriction but not preeclampsia. Placenta 31:197–202

    CAS  Article  PubMed  Google Scholar 

  101. 101.

    Janssen AB, Tunster SJ, Savory N, Holmes A, Beasley J, Parveen, SAR, Penketh, RJA, John RM (2015) Placental expression of imprinted genes varies with sampling site and mode of delivery. Placenta 36:790–795

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  102. 102.

    Romanelli V, Belinchón A, Campos-Barros A, Heath KE, García-Miñaur S, Martínez-Glez V, Palomo R, Mercado G, Gracia R et al (2009) Cdkn1c mutations in hellp/preeclamptic mothers of beckwith–wiedemann syndrome (bws) patients. Placenta 30:551–554

    CAS  Article  PubMed  Google Scholar 

  103. 103.

    Kanayama N (2002) Deficiency in p57kip2 expression induces preeclampsia-like symptoms in mice. Mol Hum Reprod 8:1129–1135

    CAS  Article  PubMed  Google Scholar 

  104. 104.

    Knox KS, Baker JC (2007) Genome-wide expression profiling of placentas in the p57kip2 model of pre-eclampsia. Mol Hum Reprod 13:251–263

    CAS  Article  PubMed  Google Scholar 

  105. 105.

    Takahashi K (2000) P57kip2 regulates the proper development of labyrinthine and spongiotrophoblasts. Mol Hum Reprod 6:1019–1025

    CAS  Article  PubMed  Google Scholar 

  106. 106.

    Tunster SJ, Van de Pette M, John RM (2011) Fetal overgrowth in the cdkn1c mouse model of beckwith-wiedemann syndrome. Dis Models Mech 4:814–821

    CAS  Article  Google Scholar 

  107. 107.

    Jin F, Qiao C, Luan N, Shang T (2015) The expression of the imprinted gene pleckstrin homology-like domain family a member 2 in placental tissues of preeclampsia and its effects on the proliferation, migration and invasion of trophoblast cells jeg-3. Clin Exp Pharmacol Physiol 42:1142–1151

    CAS  Article  PubMed  Google Scholar 

  108. 108.

    Weksberg R (2010) Imprinted genes and human disease. Am J Med Genet 154C:317–320

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the NIMH Grants K01 MH080062, ARRA supplement K01 MH080062S and R01MH102729 (to YN), and MRC Grant MR/MD013960/1 (to AJ).

Author Contributions

Y Nomura: Protocol/project development, Manuscript writing/editing, Study Design; R John: Manuscript writing/editing, Placenta Biology, and Epigenetics; AB Janssen: Manuscript writing/editing, Translational Epigenetics; C Davey: Manuscript writing/editing, Critical Review; J Finik: Manuscript writing/editing, Literature Review, Literature Search; J Buthmann: Manuscript writing/editing, Literature Review, Literature Search; V Glover: Manuscript writing/editing, Critical Review; L Lambertini: Manuscript writing/editing, Translational Epigenetics.

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Correspondence to Yoko Nomura.

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Nomura, Y., John, R.M., Janssen, A.B. et al. Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes. Arch Gynecol Obstet 295, 1319–1329 (2017). https://doi.org/10.1007/s00404-017-4347-3

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Keywords

  • Genomic imprinting
  • Placenta Epigenetics
  • Preeclampsia
  • Neurobehavioral development