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Mechanisms affecting neuroendocrine and epigenetic regulation of body weight and onset of puberty: Potential implications in the child born small for gestational age (SGA)

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Abstract

Signaling peptides produced in peripheral tissues such as gut, adipose tissue, and pancreas communicate with brain centers, such as hypothalamus and hindbrain to manage energy homeostasis. These regulatory mechanisms of energy intake and storage have evolved during long periods of hunger in the evolution of man to protect the species from extinction. It is now clear that these circuitries are influenced by prenatal and postnatal environmental factors including endocrine disruptive chemicals. Hypothalamic appetite regulatory systems develop and mature in utero and early infancy, and involve signaling pathways that are important also for the regulation of puberty onset. Recent studies in humans and animals have shown that metabolic pathways involved in regulation of growth, body weight gain and sexual maturation are largely affected by epigenetic programming that can impact both current and future generations. In particular, intrauterine and early infantile developmental phases of high plasticity are susceptible to factors that affect metabolic programming that therefore, affect metabolic function throughout life. In children born small for gestational age, poor nutritional conditions during gestation can modify metabolic systems to adapt to expectations of chronic undernutrition. These children are potentially poorly equipped to cope with energy-dense diets and are possibly programmed to store as much energy as possible, leading to later obesity, metabolic syndrome, disturbed regulation of normal puberty and early onset of cardiovascular disease. Most cases of disturbed energy balance are likely a result of a combination of genetics, epigenetics and environment. This review will discuss potential mechanisms linking intrauterine growth retardation with changes in growth, energy homeostasis and sexual maturation.

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References

  1. Hernandez MI, Mericq V. Impact of being born small for gestational age on onset and progression of puberty. Best Pract Res Clin Endocrinol Metab. 2008;22:463–76.

    PubMed  Google Scholar 

  2. Ranke MB, Cutfield WS, Lindberg A, Cowell CT, Albertsson-Wikland K, Reiter EO, et al. A growth prediction model for short children born small for gestational age. J Pediatr Endocrinol Metab. 2002;15 Suppl 5:1273.

    PubMed  Google Scholar 

  3. Ibanez L, Potau N, Marcos MV, de Zegher F. Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J Clin Endocrinol Metab. 1999;84:4739–41.

    PubMed  CAS  Google Scholar 

  4. van Weissenbruch MM, de Waal HA Delemarre-van. Early influences on the tempo of puberty. Horm Res. 2006;65 Suppl 3:105–11.

    PubMed  Google Scholar 

  5. Main KM, Jensen RB, Asklund C, Hoi-Hansen CE, Skakkebaek NE. Low birth weight and male reproductive function. Horm Res. 2006;65 Suppl 3:116–22.

    PubMed  CAS  Google Scholar 

  6. Martinez-Aguayo A, Capurro T, Pena V, Iniguez G, Hernandez MI, Avila A, et al. Comparison of leptin levels, body composition and insulin sensitivity and secretion by OGTT in healthy, early pubertal girls born at either appropriate- or small-for-gestational age. Clin Endocrinol (Oxf). 2007;67:526–32.

    CAS  Google Scholar 

  7. Hofman PL, Cutfield WS. Insulin sensitivity in people born pre-term, with low or very low birth weight and small for gestational age. J Endocrinol Invest. 2006;29:2–8.

    PubMed  CAS  Google Scholar 

  8. Cutfield WS, Hofman PL, Mitchell M, Morison IM. Could epigenetics play a role in the developmental origins of health and disease? Pediatr Res. 2007;61:68R–75R.

    PubMed  Google Scholar 

  9. Evagelidou EN, Giapros VI, Challa AS, Kiortsis DN, Tsatsoulis AA, Andronikou SK. Serum adiponectin levels, insulin resistance, and lipid profile in children born small for gestational age are affected by the severity of growth retardation at birth. Eur J Endocrinol. 2007;156:271–7.

    PubMed  CAS  Google Scholar 

  10. Schwartz MW, Woods SC, Porte Jr D, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature. 2000;404:661–71.

    PubMed  CAS  Google Scholar 

  11. Cota D, Proulx K, Smith KA, Kozma SC, Thomas G, Woods SC, et al. Hypothalamic mTOR signaling regulates food intake. Science. 2006;312:927–30.

    PubMed  CAS  Google Scholar 

  12. Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW. Central nervous system control of food intake and body weight. Nature. 2006;443:289–95.

    PubMed  CAS  Google Scholar 

  13. Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, Zhang CY, et al. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature. 2007;449:228–32.

    PubMed  CAS  Google Scholar 

  14. Schwartz MW, Gelling RW. Rats lighten up with MCH antagonist. Nat Med. 2002;8:779–81.

    PubMed  CAS  Google Scholar 

  15. Bai FL, Yamano M, Shiotani Y, Emson PC, Smith AD, Powell JF, et al. An arcuato-paraventricular and -dorsomedial hypothalamic neuropeptide Y-containing system which lacks noradrenaline in the rat. Brain Res. 1985;331:172–5.

    PubMed  CAS  Google Scholar 

  16. Kerkerian L, Pelletier G. Effects of monosodium L-glutamate administration on neuropeptide Y-containing neurons in the rat hypothalamus. Brain Res. 1986;369:388–90.

    PubMed  CAS  Google Scholar 

  17. Berthoud HR, Morrison C. The brain, appetite, and obesity. Annu Rev Psychol. 2008;59:55–92.

    PubMed  Google Scholar 

  18. Komori T, Morikawa Y, Nanjo K, Senba E. Induction of brain-derived neurotrophic factor by leptin in the ventromedial hypothalamus. Neuroscience. 2006;139:1107–15.

    PubMed  CAS  Google Scholar 

  19. Melnick I, Pronchuk N, Cowley MA, Grove KL, Colmers WF. Developmental switch in neuropeptide Y and melanocortin effects in the paraventricular nucleus of the hypothalamus. Neuron. 2007;56:1103–15.

    PubMed  CAS  Google Scholar 

  20. Barker DJ, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet. 1986;1:1077–81.

    PubMed  CAS  Google Scholar 

  21. Stefan Y, Grasso S, Perrelet A, Orci L. A quantitative immunofluorescent study of the endocrine cell populations in the developing human pancreas. Diabetes. 1983;32:293–301.

    PubMed  CAS  Google Scholar 

  22. Breant B, Gesina E, Blondeau B. Nutrition, glucocorticoids and pancreas development. Horm Res. 2006;65 Suppl 3:98–104.

    PubMed  CAS  Google Scholar 

  23. Ackermann AM, Gannon M. Molecular regulation of pancreatic beta-cell mass development, maintenance, and expansion. J Mol Endocrinol. 2007;38:193–206.

    PubMed  CAS  Google Scholar 

  24. Harder T, Bergmann R, Kallischnigg G, Plagemann A. Duration of breastfeeding and risk of overweight: a meta-analysis. Am J Epidemiol. 2005;162:397–403.

    PubMed  Google Scholar 

  25. Dulloo AG. Thrifty energy metabolism in catch-up growth trajectories to insulin and leptin resistance. Best Pract Res Clin Endocrinol Metab. 2008;22:155–71.

    PubMed  CAS  Google Scholar 

  26. Duffield JA, Vuocolo T, Tellam R, McFarlane JR, Kauter KG, Muhlhausler BS, et al. Intrauterine growth restriction and the sex specific programming of leptin and peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA expression in visceral fat in the lamb. Pediatr Res. 2009;66:59–65.

    PubMed  CAS  Google Scholar 

  27. Barker DJ. The developmental origins of adult disease. J Am Coll Nutr. 2004;23:588S–95S.

    PubMed  CAS  Google Scholar 

  28. Catalano PM, Thomas A, Huston-Presley L, Amini SB. Increased fetal adiposity: a very sensitive marker of abnormal in utero development. Am J Obstet Gynecol. 2003;189:1698–704.

    PubMed  Google Scholar 

  29. Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA. Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics. 2003;111:e221–6.

    PubMed  Google Scholar 

  30. Ibanez L, Ong K, Dunger DB, de Zegher F. Early development of adiposity and insulin resistance after catch-up weight gain in small-for-gestational-age children. J Clin Endocrinol Metab. 2006;91:2153–8.

    PubMed  CAS  Google Scholar 

  31. Parsons TJ, Power C, Manor O. Fetal and early life growth and body mass index from birth to early adulthood in 1958 British cohort: longitudinal study. BMJ. 2001;323:1331–5.

    PubMed  CAS  Google Scholar 

  32. Loos RJ, Beunen G, Fagard R, Derom C, Vlietinck R. Birth weight and body composition in young women: a prospective twin study. Am J Clin Nutr. 2002;75:676–82.

    PubMed  CAS  Google Scholar 

  33. Passos MC, Toste FP, Dutra SC, Trotta PA, Lisboa PC, de Moura EG. Role of neonatal hyperleptinaemia on serum adiponectin and suppressor of cytokine signalling-3 expression in young rats. Br J Nutr. 2009;101:250–6.

    PubMed  CAS  Google Scholar 

  34. Plagemann A, Harder T, Janert U, Rake A, Rittel F, Rohde W, et al. Malformations of hypothalamic nuclei in hyperinsulinemic offspring of rats with gestational diabetes. Dev Neurosci. 1999;21:58–67.

    PubMed  CAS  Google Scholar 

  35. Miles JL, Huber K, Thompson NM, Davison M, Breier BH. Moderate daily exercise activates metabolic flexibility to prevent prenatally induced obesity. Endocrinology. 2009;150:179–86.

    PubMed  CAS  Google Scholar 

  36. Puglianiello A, Germani D, Cianfarani S. Exposure to uteroplacental insufficiency reduces the expression of signal transducer and activator of transcription 3 and proopiomelanocortin in the hypothalamus of newborn rats. Pediatr Res. 2009;66:208–11.

    PubMed  CAS  Google Scholar 

  37. Simmons RA, Templeton LJ, Gertz SJ. Intrauterine growth retardation leads to the development of type 2 diabetes in the rat. Diabetes. 2001;50:2279–86.

    PubMed  CAS  Google Scholar 

  38. Rajakumar PA, He J, Simmons RA, Devaskar SU. Effect of uteroplacental insufficiency upon brain neuropeptide Y and corticotropin-releasing factor gene expression and concentrations. Pediatr Res. 1998;44:168–74.

    PubMed  CAS  Google Scholar 

  39. Peterside IE, Selak MA, Simmons RA. Impaired oxidative phosphorylation in hepatic mitochondria in growth-retarded rats. Am J Physiol Endocrinol Metab. 2003;285:E1258–66.

    PubMed  CAS  Google Scholar 

  40. Thaler JP, Schwartz MW. Minireview: inflammation and obesity pathogenesis: the hypothalamus heats up. Endocrinology. 2010;151:4109–15.

    PubMed  CAS  Google Scholar 

  41. Posey KA, Clegg DJ, Printz RL, Byun J, Morton GJ, Vivekanandan-Giri A, et al. Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet. Am J Physiol Endocrinol Metab. 2009;296:E1003–12.

    PubMed  CAS  Google Scholar 

  42. Glavas MM, Kirigiti MA, Xiao XQ, Enriori PJ, Fisher SK, Evans AE, et al. Early overnutrition results in early-onset arcuate leptin resistance and increased sensitivity to high-fat diet. Endocrinology. 2010;151:1598–610.

    PubMed  CAS  Google Scholar 

  43. Roth CL, Bongiovanni KD, Gohlke B, Woelfle J. Changes in dynamic insulin and gastrointestinal hormone secretion in obese children. J Pediatr Endocrinol Metab. 2010;23:1299–309.

    PubMed  CAS  Google Scholar 

  44. Gohlke BC, Huber A, Hecher K, Fimmers R, Bartmann P, Roth CL. Fetal insulin-like growth factor (IGF)-I, IGF-II, and ghrelin in association with birth weight and postnatal growth in monozygotic twins with discordant growth. J Clin Endocrinol Metab. 2005;90:2270–4.

    PubMed  CAS  Google Scholar 

  45. Gohlke BC, Bartmann P, Fimmers R, Huber A, Hecher K, Roth CL. Fetal adiponectin and resistin in correlation with birth weight difference in monozygotic twins with discordant growth. Horm Res. 2008;69:37–44.

    PubMed  CAS  Google Scholar 

  46. Gohlke BC, Huber A, Bartmann P, Fimmers R, Hecher K, Bouret SG, et al. Cord blood leptin and IGF-I in relation to birth weight differences and head circumference in monozygotic twins. J Pediatr Endocrinol Metab. 2006;19:3–9.

    PubMed  CAS  Google Scholar 

  47. Bouret SG, Gorski JN, Patterson CM, Chen S, Levin BE, Simerly RB. Hypothalamic neural projections are permanently disrupted in diet-induced obese rats. Cell Metab. 2008;7:179–85.

    PubMed  CAS  Google Scholar 

  48. Bourguignon JP, Gerard A, Franchimont P. Maturation of the hypothalamic control of pulsatile gonadotropin-releasing hormone secretion at onset of puberty: II. Reduced potency of an inhibitory autofeedback. Endocrinology. 1990;127:2884–90.

    PubMed  CAS  Google Scholar 

  49. Bourguignon JP, Gerard A, Mathieu J, Mathieu A, Franchimont P. Maturation of the hypothalamic control of pulsatile gonadotropin-releasing hormone secretion at onset of puberty. I. Increased activation of N-methyl-D-aspartate receptors. Endocrinology. 1990;127:873–81.

    PubMed  CAS  Google Scholar 

  50. Ojeda SR, Lomniczi A, Mastronardi C, Heger S, Roth C, Parent AS, et al. Minireview: the neuroendocrine regulation of puberty: is the time ripe for a systems biology approach? Endocrinology. 2006;147:1166–74.

    PubMed  CAS  Google Scholar 

  51. Ojeda SR, Roth C, Mungenast A, Heger S, Mastronardi C, Parent AS, et al. Neuroendocrine mechanisms controlling female puberty: new approaches, new concepts. Int J Androl. 2006;29:256–63. discussion 286-290.

    PubMed  CAS  Google Scholar 

  52. Bourguignon JP, Gerard A, Alvarez Gonzalez ML, Franchimont P. Neuroendocrine mechanism of onset of puberty. Sequential reduction in activity of inhibitory and facilitatory N-methyl-D-aspartate receptors. J Clin Invest. 1992;90:1736–44.

    PubMed  CAS  Google Scholar 

  53. Terasawa E, Fernandez DL. Neurobiological mechanisms of the onset of puberty in primates. Endocr Rev. 2001;22:111–51.

    PubMed  CAS  Google Scholar 

  54. Wuttke W, Honma K, Lamberts R, Hohn KG. The role of monoamines in female puberty. Fed Proc. 1980;39:2378–83.

    PubMed  CAS  Google Scholar 

  55. Wildt L, Marshall G, Knobil E. Experimental induction of puberty in the infantile female rhesus monkey. Science. 1980;207:1373–5.

    PubMed  CAS  Google Scholar 

  56. Plant TM. The role of KiSS-1 in the regulation of puberty in higher primates. Eur J Endocrinol. 2006;155 Suppl 1:S11–6.

    PubMed  CAS  Google Scholar 

  57. Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM. Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci U S A. 2005;102:2129–34.

    PubMed  CAS  Google Scholar 

  58. El Majdoubi M, Sahu A, Ramaswamy S, Plant TM. Neuropeptide Y: a hypothalamic brake restraining the onset of puberty in primates. Proc Natl Acad Sci U S A. 2000;97:6179–84.

    PubMed  Google Scholar 

  59. Plant TM. Leptin, growth hormone, and the onset of primate puberty. J Clin Endocrinol Metab. 2001;86:458–60.

    PubMed  CAS  Google Scholar 

  60. Keen KL, Burich AJ, Mitsushima D, Kasuya E, Terasawa E. Effects of pulsatile infusion of the GABA(A) receptor blocker bicuculline on the onset of puberty in female rhesus monkeys. Endocrinology. 1999;140:5257–66.

    PubMed  CAS  Google Scholar 

  61. Terasawa E. Role of GABA in the mechanism of the onset of puberty in non-human primates. Int Rev Neurobiol. 2005;71:113–29.

    PubMed  CAS  Google Scholar 

  62. Ojeda SR, Lomniczi A, Loche A, Matagne V, Kaidar G, Sandau US, et al. The transcriptional control of female puberty. Brain Res. 2010;1364:164–74.

    PubMed  CAS  Google Scholar 

  63. Ojeda SR, Lomniczi A, Sandau U, Matagne V. New concepts on the control of the onset of puberty. Endocr Dev. 2010;17:44–51.

    PubMed  CAS  Google Scholar 

  64. Pierroz DD, Aebi AC, Huhtaniemi IT, Aubert ML. Many LH peaks are needed to physiologically stimulate testosterone secretion: modulation by fasting and NPY. Am J Physiol. 1999;276:E603–10.

    PubMed  CAS  Google Scholar 

  65. Hiney JK, Srivastava V, Nyberg CL, Ojeda SR, Dees WL. Insulin-like growth factor I of peripheral origin acts centrally to accelerate the initiation of female puberty. Endocrinology. 1996;137:3717–28.

    PubMed  CAS  Google Scholar 

  66. Casanueva FF, Dieguez C. Neuroendocrine regulation and actions of leptin. Front Neuroendocrinol. 1999;20:317–63.

    PubMed  CAS  Google Scholar 

  67. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999;341:879–84.

    PubMed  CAS  Google Scholar 

  68. Licinio J, Caglayan S, Ozata M, Yildiz BO, de Miranda PB, O'Kirwan F, et al. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc Natl Acad Sci U S A. 2004;101:4531–6.

    PubMed  CAS  Google Scholar 

  69. Clayton PE, Trueman JA. Leptin and puberty. Arch Dis Child. 2000;83:1–4.

    PubMed  CAS  Google Scholar 

  70. Lindemans M, Liu F, Janssen T, Husson SJ, Mertens I, Gade G, et al. Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2009;106:1642–7.

    PubMed  CAS  Google Scholar 

  71. Roth CL, Mastronardi C, Lomniczi A, Wright H, Cabrera R, Mungenast AE, et al. Expression of a tumor-related gene network increases in the mammalian hypothalamus at the time of female puberty. Endocrinology. 2007;148:5147–61.

    PubMed  CAS  Google Scholar 

  72. Ojeda SR, Dubay C, Lomniczi A, Kaidar G, Matagne V, Sandau US, et al. Gene networks and the neuroendocrine regulation of puberty. Mol Cell Endocrinol. 2010;324:3–11.

    PubMed  CAS  Google Scholar 

  73. Morris DH, Jones ME, Schoemaker MJ, Ashworth A, Swerdlow AJ. Familial concordance for age at menarche: analyses from the Breakthrough Generations Study. Paediatr Perinat Epidemiol. 2011;25:306–11.

    PubMed  Google Scholar 

  74. Elks CE, Perry JR, Sulem P, Chasman DI, Franceschini N, He C, et al. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nat Genet. 2010;42:1077–85.

    PubMed  CAS  Google Scholar 

  75. Sulem P, Gudbjartsson DF, Rafnar T, Holm H, Olafsdottir EJ, Olafsdottir GH, et al. Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche. Nat Genet. 2009;41:734–8.

    PubMed  CAS  Google Scholar 

  76. Viswanathan SR, Daley GQ, Gregory RI. Selective blockade of microRNA processing by Lin28. Science. 2008;320:97–100.

    PubMed  CAS  Google Scholar 

  77. Nimmo RA, Slack FJ. An elegant miRror: microRNAs in stem cells, developmental timing and cancer. Chromosoma. 2009;118:405–18.

    PubMed  CAS  Google Scholar 

  78. Hartge P. Genetics of reproductive lifespan. Nat Genet. 2009;41:637–8.

    PubMed  CAS  Google Scholar 

  79. Chesler EJ, Lu L, Shou S, Qu Y, Gu J, Wang J, et al. Complex trait analysis of gene expression uncovers polygenic and pleiotropic networks that modulate nervous system function. Nat Genet. 2005;37:233–42.

    PubMed  CAS  Google Scholar 

  80. Hinney A, Vogel CI, Hebebrand J. From monogenic to polygenic obesity: recent advances. Eur Child Adolesc Psychiatry. 2010;19:297–310.

    PubMed  Google Scholar 

  81. Elks CE, Loos RJ, Sharp SJ, Langenberg C, Ring SM, Timpson NJ, et al. Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. PLoS Med. 2010;7:e1000284.

    PubMed  Google Scholar 

  82. Heerwagen MJ, Miller MR, Barbour LA, Friedman JE. Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol Regul Integr Comp Physiol. 2010;299:R711–22.

    PubMed  CAS  Google Scholar 

  83. Barker DJ. Developmental origins of adult health and disease. J Epidemiol Community Health. 2004;58:114–5.

    PubMed  CAS  Google Scholar 

  84. Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr. 2007;27:363–88.

    PubMed  CAS  Google Scholar 

  85. Jirtle RL, Skinner MK. Environmental epigenomics and disease susceptibility. Nat Rev Genet. 2007;8:253–62.

    PubMed  CAS  Google Scholar 

  86. Reik W, Walter J. Genomic imprinting: parental influence on the genome. Nat Rev Genet. 2001;2:21–32.

    PubMed  CAS  Google Scholar 

  87. Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004;429:457–63.

    PubMed  CAS  Google Scholar 

  88. McAllister EJ, Dhurandhar NV, Keith SW, Aronne LJ, Barger J, Baskin M, et al. Ten putative contributors to the obesity epidemic. Crit Rev Food Sci Nutr. 2009;49:868–913.

    PubMed  Google Scholar 

  89. Baccarelli A, Bollati V. Epigenetics and environmental chemicals. Curr Opin Pediatr. 2009;21:243–51.

    PubMed  Google Scholar 

  90. Ke X, Lei Q, James SJ, Kelleher SL, Melnyk S, Jernigan S, et al. Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats. Physiol Genomics. 2006;25:16–28.

    PubMed  CAS  Google Scholar 

  91. Joss-Moore LA, Lane RH. The developmental origins of adult disease. Curr Opin Pediatr. 2009;21:230–4.

    PubMed  Google Scholar 

  92. Stoffers DA, Desai BM, DeLeon DD, Simmons RA. Neonatal exendin-4 prevents the development of diabetes in the intrauterine growth retarded rat. Diabetes. 2003;52:734–40.

    PubMed  CAS  Google Scholar 

  93. Park JH, Stoffers DA, Nicholls RD, Simmons RA. Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Invest. 2008;118:2316–24.

    PubMed  CAS  Google Scholar 

  94. Luo ZC, Low LC, Karlberg J. Critical growth phases for adult shortness in Hong Kong Chinese. J Pediatr Endocrinol Metab. 2001;14:757–65.

    PubMed  CAS  Google Scholar 

  95. Kappeler L, De Magalhaes Filho C, Leneuve P, Xu J, Brunel N, Chatziantoniou C, et al. Early postnatal nutrition determines somatotropic function in mice. Endocrinology. 2009;150:314–23.

    PubMed  CAS  Google Scholar 

  96. Fu Q, Yu X, Callaway CW, Lane RH, McKnight RA. Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF-1 gene. Faseb J. 2009;23:2438–49.

    PubMed  CAS  Google Scholar 

  97. Nativio R, Sparago A, Ito Y, Weksberg R, Riccio A, Murrell A. Disruption of genomic neighbourhood at the imprinted IGF2-H19 locus in Beckwith-Wiedemann syndrome and Silver-Russell syndrome. Hum Mol Genet. 2011;20:1363–74.

    PubMed  CAS  Google Scholar 

  98. Netchine I, Rossignol S, Dufourg MN, Azzi S, Rousseau A, Perin L, et al. 11p15 imprinting center region 1 loss of methylation is a common and specific cause of typical Russell-Silver syndrome: clinical scoring system and epigenetic-phenotypic correlations. J Clin Endocrinol Metab. 2007;92:3148–54.

    PubMed  CAS  Google Scholar 

  99. Demars J, Rossignol S, Netchine I, Syin Lee K, Shmela M, Faivre L, et al. New insights into the pathogenesis of Beckwith-Wiedemann and Silver-Russell syndromes: Contribution of small copy number variations to 11p15 imprinting defects. Hum Mutat. 2011

  100. Garcia-Bassets I, Kwon YS, Telese F, Prefontaine GG, Hutt KR, Cheng CS, et al. Histone methylation-dependent mechanisms impose ligand dependency for gene activation by nuclear receptors. Cell. 2007;128:505–18.

    PubMed  CAS  Google Scholar 

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

  102. Anway MD, Leathers C, Skinner MK. Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. Endocrinology. 2006;147:5515–23.

    PubMed  CAS  Google Scholar 

  103. Janesick A, Blumberg B. Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity. Birth Defects Res C Embryo Today 93:34–50

  104. Newbold RR, Jefferson WN, Padilla-Banks E, Haseman J. Developmental exposure to diethylstilbestrol (DES) alters uterine response to estrogens in prepubescent mice: low versus high dose effects. Reprod Toxicol. 2004;18:399–406.

    PubMed  CAS  Google Scholar 

  105. Newbold RR, Padilla-Banks E, Jefferson WN. Environmental estrogens and obesity. Mol Cell Endocrinol. 2009;304:84–9.

    PubMed  CAS  Google Scholar 

  106. Rubin BS, Murray MK, Damassa DA, King JC, Soto AM. Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels. Environ Health Perspect. 2001;109:675–80.

    PubMed  CAS  Google Scholar 

  107. Stahlhut RW, van Wijngaarden E, Dye TD, Cook S, Swan SH. Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males. Environ Health Perspect. 2007;115:876–82.

    PubMed  CAS  Google Scholar 

  108. Verhulst SL, Nelen V, Hond ED, Koppen G, Beunckens C, Vael C, et al. Intrauterine exposure to environmental pollutants and body mass index during the first 3 years of life. Environ Health Perspect. 2009;117:122–6.

    PubMed  CAS  Google Scholar 

  109. Somm E, Schwitzgebel VM, Toulotte A, Cederroth CR, Combescure C, Nef S, et al. Perinatal exposure to bisphenol a alters early adipogenesis in the rat. Environ Health Perspect. 2009;117:1549–55.

    PubMed  CAS  Google Scholar 

  110. Sun Y, Nakashima MN, Takahashi M, Kuroda N, Nakashima K. Determination of bisphenol A in rat brain by microdialysis and column switching high-performance liquid chromatography with fluorescence detection. Biomed Chromatogr. 2002;16:319–26.

    PubMed  CAS  Google Scholar 

  111. Zoeller RT, Bansal R, Parris C. Bisphenol-A, an environmental contaminant that acts as a thyroid hormone receptor antagonist in vitro, increases serum thyroxine, and alters RC3/neurogranin expression in the developing rat brain. Endocrinology. 2005;146:607–12.

    PubMed  CAS  Google Scholar 

  112. Savabieasfahani M, Kannan K, Astapova O, Evans NP, Padmanabhan V. Developmental programming: differential effects of prenatal exposure to bisphenol-A or methoxychlor on reproductive function. Endocrinology. 2006;147:5956–66.

    PubMed  CAS  Google Scholar 

  113. Grun F, Blumberg B. Endocrine disrupters as obesogens. Mol Cell Endocrinol. 2009;304:19–29.

    PubMed  Google Scholar 

  114. Itsuki-Yoneda A, Kimoto M, Tsuji H, Hiemori M, Yamashita H. Effect of a hypolipidemic drug, Di (2-ethylhexyl) phthalate, on mRNA-expression associated fatty acid and acetate metabolism in rat tissues. Biosci Biotechnol Biochem. 2007;71:414–20.

    PubMed  CAS  Google Scholar 

  115. Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect. 2006;114:567–72.

    PubMed  CAS  Google Scholar 

  116. Buck Louis GM, Gray Jr LE, Marcus M, Ojeda SR, Pescovitz OH, Witchel SF, et al. Environmental factors and puberty timing: expert panel research needs. Pediatrics. 2008;121 Suppl 3:S192–207.

    PubMed  Google Scholar 

  117. Parent AS, Rasier G, Gerard A, Heger S, Roth C, Mastronardi C, et al. Early onset of puberty: tracking genetic and environmental factors. Horm Res. 2005;64 Suppl 2:41–7.

    PubMed  CAS  Google Scholar 

  118. Crews D, McLachlan JA. Epigenetics, evolution, endocrine disruption, health, and disease. Endocrinology. 2006;147:S4–S10.

    PubMed  CAS  Google Scholar 

  119. Ozen S, Darcan S: Effects of environmental endocrine disruptors on pubertal development. J Clin Res Pediatr Endocrinol. 3:1–6

  120. Mouritsen A, Aksglaede L, Sorensen K, Mogensen SS, Leffers H, Main KM, et al. Hypothesis: exposure to endocrine-disrupting chemicals may interfere with timing of puberty. Int J Androl. 33:346–359

  121. Rasier G, Parent AS, Gerard A, Denooz R, Lebrethon MC, Charlier C, et al. Mechanisms of interaction of endocrine-disrupting chemicals with glutamate-evoked secretion of gonadotropin-releasing hormone. Toxicol Sci. 2008;102:33–41.

    PubMed  CAS  Google Scholar 

  122. Patisaul HB, Todd KL, Mickens JA, Adewale HB. Impact of neonatal exposure to the ERalpha agonist PPT, bisphenol-A or phytoestrogens on hypothalamic kisspeptin fiber density in male and female rats. Neurotoxicology. 2009;30:350–7.

    PubMed  CAS  Google Scholar 

  123. Titus-Ernstoff L, Troisi R, Hatch EE, Palmer JR, Hyer M, Kaufman R, et al. Birth defects in the sons and daughters of women who were exposed in utero to diethylstilbestrol (DES). Int J Androl. 33:377–384

  124. Hatch EE, Troisi R, Wise LA, Titus-Ernstoff L, Hyer M, Palmer JR, et al. Preterm birth, fetal growth, and age at menarche among women exposed prenatally to diethylstilbestrol (DES). Reprod Toxicol. 31:151–157

  125. Roth CL, Ojeda SR. Genes involved in the neuroendocrine control of normal puberty and abnormal puberty of central origin. Pediatr Endocrinol Rev. 2005;3:7–16.

    Google Scholar 

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Roth, C.L., Sathyanarayana, S. Mechanisms affecting neuroendocrine and epigenetic regulation of body weight and onset of puberty: Potential implications in the child born small for gestational age (SGA). Rev Endocr Metab Disord 13, 129–140 (2012). https://doi.org/10.1007/s11154-012-9212-x

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