title: Epigenomics, gestational programming and risk of metabolic syndrome.
abstract: Epigenetic mechanisms are emerging as mediators linking early environmental exposures during pregnancy with programmed changes in gene expression that alter offspring growth and development. There is irrefutable evidence from human and animal studies that nutrient and environmental agent exposures (for example, endocrine disruptors) during pregnancy may affect fetal/newborn development resulting in offspring obesity and obesity-associated metabolic abnormalities (metabolic syndrome). This concept of 'gestational programming' is associated with alterations to the epigenome (nongenomic) rather than changes in the DNA sequence (genomic). Epigenetic alterations induced by suboptimal maternal nutrition/endocrine factors include DNA methylation, histone modifications, chromatin remodeling and/or regulatory feedback by microRNAs, all of which have the ability to modulate gene expression and promote the metabolic syndrome phenotype. Recent studies have shown tissue-specific transcriptome patterns and phenotypes not only in the exposed individual, but also in subsequent progeny. Notably, the transmission of gestational programming effects to subsequent generations occurs in the absence of continued adverse environmental exposures, thus propagating the cycle of obesity and metabolic syndrome. This phenomenon may be attributed to an extrinsic process resulting from the maternal phenotype and the associated nutrient alterations occurring within each pregnancy. In addition, epigenetic inheritance may occur through somatic cells or through the germ line involving both maternal and paternal lineages. Since epigenetic gene modifications may be reversible, understanding how epigenetic mechanisms contribute to transgenerational transmission of obesity and metabolic dysfunction is crucial for the development of novel early detection and prevention strategies for programmed metabolic syndrome. In this review we discuss the evidence in human and animal studies for the role of epigenomic mechanisms in the transgenerational transmission of programmed obesity and metabolic syndrome.
authors: 1] Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Perinatal Research Laboratories, Torrance, CA, USA [2] Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors: M
authors: M
authors: Desai
authors: 1] Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Perinatal Research Laboratories, Torrance, CA, USA [2] Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors: J K
authors: JK
authors: Jellyman
authors: 1] Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Perinatal Research Laboratories, Torrance, CA, USA [2] Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors: M G
authors: MG
authors: Ross
mesh_terms: D000818:Animals; D019175:DNA Methylation; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004781:Environmental Exposure; D057890:Epigenomics; D005260:Female; D047109:Fetal Development / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D039382:Maternal Nutritional Physiological Phenomena / Q000235:genetics*; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000235:genetics*; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D012306:Risk
references: Curr Opin Clin Nutr Metab Care. 2012 Jul;15(4):342-9
references: 22617562
references: JAMA. 2012 Feb 1;307(5):483-90
references: 22253364
references: Am J Physiol Gastrointest Liver Physiol. 2010 Nov;299(5):G1023-9
references: 20813916
references: J Pathol. 2010 Jan;220(2):126-39
references: 19882673
references: PLoS One. 2008;3(11):e3745
references: 19015723
references: Trends Biochem Sci. 2011 May;36(5):272-81
references: 21315607
references: Int J Obes Relat Metab Disord. 2004 Nov;28 Suppl 3:S46-53
references: 15543219
references: J Zhejiang Univ Sci B. 2014 Sep;15(9):820-9
references: 25183036
references: Pediatrics. 2005 Mar;115(3):e290-6
references: 15741354
references: J Dev Orig Health Dis. 2010 Dec;1(6):412-8
references: 25142012
references: Biol Rev Camb Philos Soc. 1997 May;72(2):329-48
references: 9155245
references: Diabetologia. 2011 Feb;54(2):360-7
references: 21104225
references: Int J Biochem Cell Biol. 2006;38(5-6):894-903
references: 16118061
references: FASEB J. 2013 Jun;27(6):2504-12
references: 23475851
references: Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R91-6
references: 15297266
references: Int J Obes (Lond). 2012 Oct;36(10):1320-4
references: 22158263
references: Nat Rev Genet. 2012 Jan 04;13(2):97-109
references: 22215131
references: Int J Obes (Lond). 2015 Apr;39(4):650-7
references: 24158121
references: Hum Biol. 2000 Aug;72(4):641-54
references: 11048791
references: Nat Rev Genet. 2007 Feb;8(2):93-103
references: 17230196
references: PLoS One. 2011 Mar 10;6(3):e16729
references: 21423737
references: Vitam Horm. 2014;94:211-27
references: 24388192
references: J Am Coll Cardiol. 2013 Aug 20;62(8):697-703
references: 23810877
references: Am J Obstet Gynecol. 2014 Sep;211(3):237.e1-237.e13
references: 24631702
references: Genes Cells. 2009 Aug;14(8):991-1001
references: 19624751
references: Ann N Y Acad Sci. 2004 Dec;1032:63-84
references: 15677396
references: J Neurosci. 2014 Aug 6;34(32):10659-74
references: 25100599
references: J Physiol Biochem. 2009 Mar;65(1):1-9
references: 19588726
references: PLoS One. 2011;6(11):e28282
references: 22140567
references: Hum Mol Genet. 2009 Nov 1;18(21):4046-53
references: 19656776
references: J Physiol. 2009 Oct 15;587(Pt 20):4963-76
references: 19723777
references: BJOG. 2012 May;119(6):716-23
references: 22489762
references: Am J Hum Genet. 2006 Jul;79(1):67-84
references: 16773567
references: Am J Clin Nutr. 2010 Feb;91(2):309-20
references: 19939982
references: Br J Nutr. 2007 Mar;97(3):435-9
references: 17313703
references: Ann Hum Biol. 2009 Sep-Oct;36(5):445-58
references: 19562567
references: Mol Cell. 2009 Mar 27;33(6):717-26
references: 19217333
references: Am J Physiol Regul Integr Comp Physiol. 2009 Aug;297(2):R291-9
references: 19458276
references: J Physiol. 2009 Feb 15;587(Pt 4):905-15
references: 19103681
references: Eur J Obstet Gynecol Reprod Biol. 1995 Jul;61(1):23-30
references: 8549843
references: Genome Biol. 2013;14(10):R115
references: 24138928
references: Nat Genet. 2011 Jun 26;43(8):753-60
references: 21706003
references: N Engl J Med. 2004 Dec 23;351(26):2683-93
references: 15616203
references: Mol Cell. 2014 Aug 7;55(3):372-82
references: 25002143
references: Am J Clin Nutr. 2008 Feb;87(2):362-9
references: 18258626
references: Curr Diab Rep. 2013 Feb;13(1):27-33
references: 23188593
references: Am J Physiol Endocrinol Metab. 2000 Jul;279(1):E83-7
references: 10893326
references: Clin Obstet Gynecol. 2013 Sep;56(3):529-36
references: 23751877
references: PLoS One. 2011;6(5):e17711
references: 21637341
references: Eur J Epidemiol. 2012 Jan;27(1):53-61
references: 22187263
references: J Nutr. 1984 Aug;114(8):1484-92
references: 6540299
references: Przegl Epidemiol. 2011;65(3):497-502
references: 22184955
references: Epigenomics. 2011 Feb;3(1):59-72
references: 22126153
references: Horm Res. 2006;65 Suppl 3:65-9
references: 16612116
references: FASEB J. 2007 Oct;21(12):3380-5
references: 17551099
references: Semin Reprod Med. 2011 May;29(3):237-45
references: 21710399
references: Paediatr Perinat Epidemiol. 1992 Apr;6(2):240-53
references: 1584725
references: Clin Exp Pharmacol Physiol. 2006 Apr;33(4):395-9
references: 16620308
references: Clin Epigenetics. 2013 Sep 03;5(1):15
references: 24004477
references: Environ Mol Mutagen. 2008 Jan;49(1):4-8
references: 18172876
references: J Biol Chem. 2006 Jun 23;281(25):17180-8
references: 16613853
references: Biochem Cell Biol. 1992 Oct-Nov;70(10-11):856-66
references: 1297351
references: Nat Rev Genet. 2015 Jan;16(1):7-17
references: 25385129
references: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9
references: 16009939
references: Bioessays. 2010 Aug;32(8):659-68
references: 20658704
references: Science. 2014 Aug 15;345(6198):1255903
references: 25011554
references: Diabetes. 2011 May;60(5):1528-34
references: 21471513
references: Endocrinol Metab (Seoul). 2014 Jun;29(2):122-35
references: 25031884
references: Epigenetics. 2011 Jul;6(7):838-42
references: 21637037
references: Nat Rev Genet. 2000 Oct;1(1):11-9
references: 11262868
references: BMC Biol. 2009 Jul 10;7:38
references: 19589179
references: Obes Res. 2001 Nov;9 Suppl 4:228S-233S
references: 11707546
references: Br J Nutr. 1975 Mar;33(2):233-53
references: 1115762
references: J Obes. 2013;2013:492170
references: 23840945
references: Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11439-44
references: 23716672
references: Am J Clin Nutr. 2011 Apr;93(4):897S-900
references: 21289222
references: Obes Rev. 2002 Aug;3(3):217-24
references: 12164475
references: Biochem Biophys Res Commun. 2009 Jun 12;383(4):421-5
references: 19364493
references: Reprod Toxicol. 2008 Jan;25(1):2-6
references: 17949945
references: Int J Obes (Lond). 2010 Jan;34(1):6-17
references: 19844212
references: Hum Mol Genet. 2006 Mar 1;15(5):705-16
references: 16421170
references: Eur J Hum Genet. 2002 Nov;10(11):682-8
references: 12404098
references: Placenta. 2003 Nov;24(10):905-11
references: 14580372
references: J Clin Endocrinol Metab. 2009 Nov;94(11):4275-83
references: 19820018
references: Am J Physiol Regul Integr Comp Physiol. 2009 May;296(5):R1464-72
references: 19244583
references: Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19229-34
references: 19047629
references: Diabetes. 2009 Feb;58(2):460-8
references: 19017762
references: Am J Clin Nutr. 2005 Feb;81(2):480-7
references: 15699238
references: Curr Mol Med. 2011 Jun;11(4):304-16
references: 21506921
references: Pediatrics. 1989 Aug;84(2):343-7
references: 2748265
references: J Nutr. 2007 Jan;137(1 Suppl):223S-228S
references: 17182830
references: Adv Data. 2004 Oct 27;(347):1-17
references: 15544194
references: J Biol Chem. 2008 May 16;283(20):13611-26
references: 18326493
references: Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R34-8
references: 15178540
references: Br J Obstet Gynaecol. 1992 Jan;99(1):67-74
references: 1547177
references: Mol Cell Biol. 2007 Jul;27(14):5147-60
references: 17515611
references: Int J Biochem Cell Biol. 2009 Jan;41(1):176-84
references: 18793748
references: Genesis. 2003 Feb;35(2):88-93
references: 12533790
references: Curr Drug Targets. 2007 Aug;8(8):923-34
references: 17691929
references: Nature. 2009 Apr 9;458(7239):757-61
references: 19194461
references: Mol Cell Biol. 2003 Aug;23(15):5293-300
references: 12861015
references: Mamm Genome. 2009 Sep-Oct;20(9-10):532-43
references: 19760320
references: Curr Genomics. 2009 May;10(3):169-83
references: 19881910
references: Int J Obes (Lond). 2012 Jun;36(6):757-65
references: 21912396
references: Endocrinology. 2010 Oct;151(10):4756-64
references: 20685869
references: Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13056-61
references: 17670942
references: Curr Diab Rep. 2001 Aug;1(1):78-81
references: 12762961
references: JAMA. 2004 Oct 13;292(14):1724-37
references: 15479938
references: Int J Obes Suppl. 2012 Dec;2(Suppl 2):S14-S18
references: 25018872
references: BMC Res Notes. 2014 May 02;7:278
references: 24886386
references: Endocrinology. 2013 Nov;154(11):4113-25
references: 23959936
references: Biochim Biophys Acta. 2012 Jul;1819(7):727-32
references: 22240386
references: Endocrinology. 2011 Jun;152(6):2228-36
references: 21447631
references: Eur J Epidemiol. 2003;18(8):733-6
references: 12974544
references: Nat Neurosci. 2011 Aug 28;14(10):1345-51
references: 21874013
references: Physiol Genomics. 2006 Oct 11;27(2):114-21
references: 16849634
references: Asian J Androl. 2013 Jul;15(4):451-2
references: 23749000
references: Clin Sci (Lond). 2008 Mar;114(5):381-92
references: 17927565
references: Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):716-21
references: 18184812
references: JAMA. 2014 Feb 26;311(8):806-14
references: 24570244
references: Diabetes. 2013 Nov;62(11):3727-35
references: 23884886
references: J Nutr. 2000 Apr;130(4):741-4
references: 10736323
references: Epigenetics. 2013 Jul;8(7):710-9
references: 23803567
references: Diabetes. 1999 Apr;48(4):685-90
references: 10102682
references: Genome Res. 2012 Apr;22(4):633-41
references: 22357612
references: BMC Med. 2013 Feb 06;11:29
references: 23388414
references: BMC Cell Biol. 2007 May 29;8:18
references: 17535427
references: J Physiol. 2005 Jul 1;566(Pt 1):225-36
references: 15860532
references: Obesity (Silver Spring). 2010 Feb;18(2):314-21
references: 19680236
references: Circulation. 2003 Sep 30;108(13):1546-51
references: 14517150
references: Expert Rev Proteomics. 2007 Aug;4(4):465-78
references: 17705705
references: Pediatrics. 2006 Dec;118(6):e1644-9
references: 17142494
references: Mol Cell Endocrinol. 2009 Jul 10;306(1-2):33-6
references: 19481683
references: Am J Clin Nutr. 2007 Oct;86(4):1219-24
references: 17921405
references: Cell Cycle. 2008 Jun 1;7(11):1529-38
references: 18469525
references: Nature. 2007 May 24;447(7143):396-8
references: 17522671
references: Obes Rev. 2005 May;6(2):143-54
references: 15836465
references: Nature. 2009 Nov 19;462(7271):315-22
references: 19829295
references: Antioxid Redox Signal. 2012 Jul 15;17(2):282-301
references: 22044276
references: Environ Mol Mutagen. 2008 Jan;49(1):83-95
references: 18095329
references: BJOG. 2008 Sep;115(10):1243-9
references: 18715409
references: Trends Biotechnol. 2009 Jan;27(1):27-36
references: 19012978
references: Int J Obes (Lond). 2011 Jan;35(1):72-83
references: 20548303
references: BMC Med. 2010 Dec 21;8:87
references: 21176133
references: Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3387-92
references: 23401553
references: Science. 2001 Aug 10;293(5532):1074-80
references: 11498575
references: Nat Genet. 1999 Nov;23(3):314-8
references: 10545949
references: Physiol Rev. 2005 Apr;85(2):571-633
references: 15788706
references: Inflamm Res. 2012 Aug;61(8):789-807
references: 22588278
references: J Zhejiang Univ Sci B. 2010 Oct;11(10):784-91
references: 20872986
references: Obstet Gynecol. 2008 Nov;112(5):999-1006
references: 18978098
references: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17308-12
references: 17101998
references: Endocrinology. 2010 Dec;151(12):5617-23
references: 20943806
references: Eur J Hum Genet. 2006 Feb;14(2):159-66
references: 16391557
references: Fertil Steril. 2008 Feb;89(2 Suppl):e41
references: 18308059
references: Am J Physiol Endocrinol Metab. 2007 May;292(5):E1270-9
references: 17213472
references: Genome Res. 2005 Jun;15(6):875-84
references: 15930497
references: Reprod Toxicol. 2011 Apr;31(3):359-62
references: 20965246
references: Diabetologia. 2006 May;49(5):1117-9
references: 16557373
references: Endocrinology. 2010 Aug;151(8):3652-64
references: 20573728
references: Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17046-9
references: 18955703
references: JAMA. 2012 Feb 1;307(5):491-7
references: 22253363
references: Obstet Gynecol. 2004 Oct;104(4):720-6
references: 15458892
references: BJOG. 2013 Apr;120(5):548-53
references: 23346894
references: FEBS Lett. 2011 Jul 7;585(13):2049-58
references: 21420958
references: PLoS One. 2011 Apr 15;6(4):e18950
references: 21526203
references: PLoS One. 2010 Feb 02;5(2):e9022
references: 20126310
references: Cell. 2007 Jun 29;129(7):1311-23
references: 17604720
references: Front Horm Res. 2008;36:73-84
references: 18230895
references: Prog Mol Biol Transl Sci. 2010;94:291-347
references: 21036330
references: Animal. 2012 Mar;6(3):375-81
references: 22436216
references: Diabetes Care. 2005 Oct;28(10):2406-11
references: 16186271