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研究生:古玫生
研究生(外文):Mei-Sheng Ku
論文名稱:胎兒暴露體與孩童發展:以印痕基因甲基化程度作為測量指標
論文名稱(外文):Fetal Exposomes and Child Development: Using DNA Methylation Levels of Imprinted Genes as an Indicator
指導教授:劉貞佑
指導教授(外文):Chen-Yu Liu
口試委員:陳美蓮蕭朱杏陳保中
口試日期:2015-07-24
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:環境衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:英文
論文頁數:103
中文關鍵詞:胎兒暴露體基因甲基化MESTPEG3印痕基因神經行為發展
外文關鍵詞:Fetal exposomesDNA methylationMESTPEG3imprinted geneneurobehavioral development
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背景
母親於懷孕時所受到的各種暴露,一直都被認為與不好的新生兒發展、孩童神經系統及行為等有關係。然而,其中的主要機制仍須進一步的闡明。印痕基因甲基化是一種重要的表基因修飾,可提供量化的篩檢指標,進而了解產前暴露對於新生兒發展、神經行為發展的影響,更甚而往後發展成某些疾病。
研究目的
本研究之目的為透過測量表基因甲基化程度,了解其與環境暴露及嬰兒出生結果、兩歲和七歲孩童神經行為發展的關連性。
方法
本研究採用2004至2005年間所蒐集的Taiwan Birth Panel Study (TBPS)世代研究族群,經篩選後共有465對母親嬰兒納入研究。由母親臍帶血及第三孕期時尿液樣本中量測共32種胎兒暴露體,包含古丁尼、18種金屬、2種有機磷殺蟲劑、4種全氟碳化物、3種酚類及4種塑化劑代謝產物,除此之外,MEST及PEG3印痕基因的甲基化是由母親臍帶血中的白血球所萃取測量。本研究使用母親產後結構性問卷、胎兒暴露體及印痕基因DNA甲基化程度等資料,運用PLS回歸分析及廣義線性混合模型,進而探討母親孕期暴露、基因甲基化以及孩童出生及神經行為發展之間的關連性。
結果
本研究於32種胎兒暴露體中,找出11種相對較重要的因子。其中,較高濃度的銅(pos1:-0.34, P=0.0357; pos3:-0.35, P=0.0277), 鉬(pos1:β= -0.38, P=0.026; pos2:β= -0.35, P=0.0358), 不同濃度的鋇(pos5: L-β=0.48, P=0.0359; M-β=0.66, P=0.0071; H-β=0.54, P=0.0322)以及全氟辛烷磺酸(L-β=-0.39, P=0.0148: H-β= -0.41, P=0.0128)均可能會改變MEST (啟動子區) 的甲基化程度,然而不同濃度的銅(L-β=0.59, P=0.0042;M-β=0.57, P=0.0075;H-β=0.64, P=0.0022),低濃度的鋅(β=0.45, P=0.0471)、鋇(β=0.51, P=0.0151)、鈷(pos3:β=-0.46, P=0.0294;pos5: β=-0.49, P= 0.032)以及低濃度古丁尼 (β=0.58, P=0.0267)也與不同程度的PEG3基因甲基化顯著有關。除此之外,本研究也發現高或低的MEST (CTCF結合區)基因甲基化都有可能增加較小嬰兒身長的風險(<Q1: OR=2.41, 95% CI=1.12-5.16; >Q3:OR=2.73, 95% CI=1.20-6.25)。另外,在調整過孩童年齡、母親教育程度、母親BMI以及胎兒小於孕期年齡等干擾因子後,MEST (啟動子區)上2個CpGs的高度甲基化也顯著較參考組的孩童行為問題的風險高(pos3: OR=4.12, 95% CI=1.34-12.66; pos4: OR=3.79, 95% CI=1.21-11.89)。同樣現象也在MEST (CTCF結合區)上低甲基化組觀察到(pos1: OR=5.02, 95% CI=1.49-16.98; pos4: OR=4.71, 95% CI=1.36-16.27)。然而,在PEG3上的某些CpGs中,高或低甲基化可能對不好的孩童神經行為發展等有保護的效果。
結論
本研究指出,在32種胎兒暴露體中,有11種是主要解釋嬰兒出生體重的因子。而這11種胎兒暴露體中,三種金屬(銅、鉬、鋇)和全氟碳化物(全氟辛烷磺酸)與MEST印痕基因甲基化程度是有關係性存在的,而四種金屬(銅、鋅、鈷、鋇)及古丁尼(尼古丁代謝產物)則與PEG3甲基化程度相關。另外,由於不同的胎兒暴露體濃度而增加或減少的印痕基因甲基化程度,都有可能對於孩童的出生結果及2歲時神經行為發展有不好的影響。


Background
In utero exposures have been suggested to be linked to adverse birth outcomes, neurodevelopment or child behavior, but the underlying mechanism remains elusive. DNA methylation, an essential epigenetic modification, of candidate imprinted genes might provide a quantitative screening marker for the effects of prenatal exposures on the development and neurobehavioral development of the infants, even the risk of developing certain disease in later life.
Objective
The objective of this study is to investigate the relationship between multiple fetal exposomes during pregnancy, epigenetic modifications and child birth and neurobehavioral outcomes at follow-up 2 and 7 years old, by quantifying DNA methylation levels of imprinted genes.
Methods
A total of 465 mother-infant pairs were included in this study from Taiwan Birth Panel Study (TBPS), collecting from 2004 to 2005. Fetal exposomes, including cotinine, 18 metals, 2 organophosphorous Pesticides, 4 perfluorinated compounds (PFCs) and 3 phenols, 4 phthalate metabolites were detected in umbilical cord blood and spot mother’s urine samples. Besides, DNA methylation levels of MEST and PEG3 imprinted gene were measured in leukocytes from umbilical cord blood. This study made use of data from structured questionnaires、fetal exposomes and DNA methylation levels to estimate the association between prenatal exposures, DNA mehtlyation levels of imprinted genes as well as child outcomes by partial least squares (PLS) regression and generalized linear mixed model.
Results
This study identified 11 relatively important factors among 32 fetal exposomes. Among these 11 exposomes, higher level group of Cu (pos1:-0.34, P=0.0357; pos3:-0.35, P=0.0277), Mo (pos1:β= -0.38, P=0.026; pos2:β= -0.35, P=0.0358), all level group of Ba (pos5: L-β=0.48, P=0.0359; M-β=0.66, P=0.0071; H-β=0.54, P=0.0322), and PFOS (L-β=-0.39, P=0.0148: H-β= -0.41, P=0.0128) were likely to alter methylation levels of MEST gene, whereas all level group of Cu (L-β=0.59, P=0.0042; M-β=0.57, P=0.0075; H-β=0.64, P=0.0022), low level group of Zn (β=0.45, P=0.0471), Ba (β=0.51, P=0.0151), Co (pos3:β=-0.46, P=0.0294; pos5: β=-0.49, P= 0.032) and low level group of cotinine (β=0.58, P=0.0267) might have differential methylation effects on PEG3 gene. Beside, hypo- or hypermethylation of MEST (CTCF binding region) might have increased risk of low birth size (<Q1: OR=2.41, 95% CI=1.12-5.16; >Q3:OR=2.73, 95% CI=1.20-6.25).Further, hypermethylation of 2 CpGs on MEST ( promoter region) gene had increased risk of having behavior problem (pos3: OR=4.12, 95% CI=1.34-12.66; pos4: OR=3.79, 95% CI=1.21-11.89), compared with reference group, after adjusting for child sex, maternal education, maternal BMI and SGA. The same phenomenon was observed in hypomethylation of position 1 and 4 of MEST (CTCF binding region) (pos1: OR=5.02, 95% CI=1.49-16.98; pos4: OR=4.71, 95% CI=1.36-16.27). At some CpGs of PEG3, hyper- or hypermethylation might have protective effects on adverse child outcomes.
Conclusion
Our study indicates that there were 11 out of 32 fetal exposomes accounting for infant birth weight. Among them, three metals (Cu、Mo、Ba) and perfluorinated compounds(PFOS) might be associated with methylation levels of MEST imprinted gene, while four metals (Cu、Zn、Co、Ba) and cotinine (metabolite of nicotine) were correlated to methylation levels of PEG3. Moreover, either the increased or decreased methylation of imprinted genes as a result of different levels of fetal exposomes was likely to have increased risk of child birth outcomes and child neurodevelopment at 2 years old.



口試委員審定書 I
致謝 II
中文摘要 III
Abstract V
Figure list X
Table list XI
Chapter 1. Introduction 1
1.1 Prenatal Exposure and Child Health Outcomes 2
1.1.1 Mother’s environmental tobacco smoke (ETS) and child growth effects 2
1.1.2 Prenatal metals exposure and child growth effects 4
1.1.3 Perfluorinated compounds (PFCs) and child growth effects 6
1.1.4 Organophosphorous pesticides and child growth effects 8
1.1.5 Phthalic acid ester (PAE), phenols and child effects 10
1.2 Genomic Imprinting 13
1.2.1 The characteristics of imprinted genes 13
1.2.2 Environmental exposure and imprinted genes 15
1.2.3 Candidate imprinted genes 17
1.3 Hypotheses and Objectives 19
Chapter 2. Materials and methods 22
2.1 Study Participants 22
2.2 Data Collection 23
2.2.1 Questionnaire, birth and neurobehavioral Outcomes 23
2.2.2 Biologic sample 25
2.2.3 Exposomes measurements 26
2.3 DNA Methylation Analysis 29
2.3.1 Bisulfite conversion 29
2.3.2 Bisulfite-converted DNA polymerase chain reaction (PCR) 31
2.3.3 Pyrosequencing 33
2.4 Statistical Methods 34
Chapter 3. Results 37
3.1 General Characteristics 37
3.2 Relatively Important Exposures in utero 45
3.3 Association Between Prenatal Exposures and Methylation Levels 47
3.3.1 MEST (promoter region) and fetal exposomes 50
3.3.2 MEST (CTCF binding region) and fetal exposomes 51
3.3.3 PEG3 and fetal exposomes 52
3.4 Association Between DNA Methylation Levels and Child Outcomes 65
3.4.1 Child birth outcomes and DNA methylation 65
3.4.2 Neonatal neurobehavioral examination, neurodevelopment outcome at 2 years old and DNA methylation 67
3.4.3 Intelligence scales and DNA methylation 69
Chapter 4. Discussion 82
Fetal exposomes and methylation levels of imprinted MEST and PEG3 gene 84
Hypomethylation or hypermethylation of imprinted genes and child outcomes 89
Limitation 91
Conclusion 92
Reference 93
Appendix 101




Apelberg BJ, Witter FR, Herbstman JB, et al. Cord serum concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in relation to weight and size at birth. Environ Health Perspect. 2007 ;115(11):1670-6.

Barton SC, Ferguson-Smith AC, Fundele R, Surani MA. Influence of paternally imprinted genes on development. Development. 1991;113(2):679-87.

Barlow DP . Genomic imprinting: a mammalian epigenetic discovery model. Annu Rev Genet, 2011; 45: 379–403.

Bouchard MF, Chevrier J, Harley KG,et al. Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environ Health Perspect 2011; 119:1189-95.

Cobbina SJ, Chen Y, Zhou Z, et al. Low concentration toxic metal mixture interactions: Effects on essential and non-essential metals in brain, liver, and kidneys of mice on sub-chronic exposure. Chemosphere. 2015;132:79-86.

Choufani S, Shapiro JS, Susiarjo M, Butcher DT, Grafodatskaya D, Lou Y. A novel approach identifies new differentially methylated regions (DMRs) associated with imprinted genes. Genome Res. 2011 ;21(3):465-76.

Coughlin SS.Toward a road map for global -omics: a primer on -omic technologies. Am J Epidemiol. 2014;180(12):1188-95.

Dejmek J, Solansk y I, Podrazilová K, Srám RJ. The exposure of nonsmoking and smoking mothers to environmental tobacco smoke during different gestational phases and fetal growth. Environ Health Perspect. 2002 ;110(6):601-6.

El Hajj N, Pliushch G, Schneider E, et al. Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus. Diabetes. 2013 Apr;62(4):1320-8.

Fei C, McLaughlin JK, Lipworth L, Olsen J. Prenatal exposure to perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) and maternally reported developmental milestones in infancy. Environ Health Perspect. 2008 ;116(10):1391-5.

Fei C, Olsen J. Prenatal exposure to perfluorinated chemicals and behavioral or coordination problems at age 7 years. Environ Health Perspect. 2011 ;119(4):573-8.

Fei DL, Koestler DC, Li Z, et al. Association between In Utero arsenic exposure, placental gene expression, and infant birth weight: a US birth cohort study. Environ Health. 2013;12:58.

Feng W, Marquez RT, Lu Z, et al. Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down-regulated in human ovariancancers by loss of heterozygosity and promoter methylation. Cancer. 2008 ;112(7):1489-502.

Falls JG, Pulford DJ, Wylie AA, Jirtle RL. Genomic imprinting: implications for human disease. Am J Pathol. 1999 ;154(3):635-47.

Goodrich JM, Sánchez BN, Dolinoy DC, et al. Quality control and statistical modeling for environmental epigenetics: A study on in utero lead exposure and DNA methylation at birth. Epigenetics. 2015 ;10(1):19-30.

Gump BB, Wu Q, Dumas AK, Kannan K. Perfluorochemical (PFC) exposure in children: associations with impaired response inhibition. Environ Sci Technol. 2011 ;45(19):8151-9.

Haggarty P, Hoad G, Campbell DM, et al. Folate in pregnancy and imprinted gene and repeat element methylation in the offspring. Am J Clin Nutr 2013 ;97(1):94-9.

Heijmans BT, Tobi EW, Stein AD et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A. 2008 ;105(44):17046-9.

Hiramuki Y, Sato T, Furuta Y, Surani MA, Sehara-Fujisawa A. Mest but Not MiR-335 Affects Skeletal Muscle Growth and Regeneration. PLoS One. 2015 22;10(6):e0130436.

Hou L, Zhang X, Wang D, Baccarelli A. Environmental chemical exposures and human epigenetics. Int J Epidemiol. 2012 ;41(1):79-105.

Hogberg J., et al. Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations. Environ. Health Perspect. 2008 ;116, 334–339.

Ivorra C, Fraga MF, Bayón GF, et al. DNA methylation patterns in newborns exposed to tobacco in utero. J Transl Med. 2015 ;13(1):25.

Jiang X, Yu Y, Yang HW, Agar NY, Frado L, Johnson MD. The imprinted gene PEG3 inhibits Wnt signaling and regulates glioma growth. J Biol Chem. 2010 ;285(11):8472-80.

Jirtle RL. Genomic imprinting and cancer. Exp Cell Res. 1999 Apr 10;248(1):18-24.

Kappil MA, Green BB, Armstrong DA, et al. Placental Expression Profile of Imprinted Genes Impacts Birth Weight. Epigenetics. 2015;17:0.

Key AP, Ferguson M, Molfese DL, Peach K, Lehman C, Molfese VJ. Smoking during pregnancy affects speech-processing ability in newborn infants. Environ Health Perspect. 2007 ;115(4):623-9.

Kharrazi M1, DeLorenze GN, Kaufman FL, Eskenazi B, Bernert JT Jr, Graham S, et al. Environmental tobacco smoke and pregnancy outcome. Epidemiology. 2004 ;15(6):660-70.

Kobayashi S, Kohda T, Miyoshi N, et al. Human PEG1/MEST, an imprinted gene on chromosome 7. Hum Mol Genet. 1997 ;6(5):781-6.

Kim YI. Nutritional epigenetics: impact of folate deficiency on DNA methylation and colon cancer susceptibility. J Nutr. 2005 ;135(11):2703-9.

Kim J, Frey WD, He H, et al. Peg3 mutational effects on reproduction and placenta-specific gene families. PLoS One. 2013;8(12):e83359.

Latini G, De Felice C, Presta G, et al. In utero exposure to di-(2-ethylhexyl)phthalate and duration of human pregnancy. Environ Health Perspect. 2003 ;111(14):1783-5.

Lauwerys R, Lison D. Health risks associated with cobalt exposure--an overview. Sci Total Environ. 1994 ;150(1-3):1-6.

LaRocca J, Binder AM, McElrath TF, Michels KB. The impact of first trimester phthalate and phenol exposure on IGF2/H19 genomic imprinting and birth outcomes. Environ Res. 2014 ;133:396-406.

Liao HT, Hsieh CJ, Chiang SY, Lin MH, Chen PC, Wu KY. Simultaneous analysis of chlorpyrifos and cypermethrin in cord blood plasma by online solid-phase extraction coupled with liquid chromatography-heated electrospray ionization tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 ;879(21):1961-6.

Lin CC, Chen YC, Su FC, et al. In utero exposure to environmental lead and manganese and neurodevelopment at 2 years of age. Environ Res. 2013 ;123:52-7.

Li J, Xiong M, Alhashem HM, et al. Effects of prenatal propofol exposure on postnatal development in rats. Neurotoxicol Teratol. 2014;43:51-8.

Liu J, Leung PW, McCauley L, Ai Y, Pinto-Martin J. Mother''s environmental tobacco smoke exposure during pregnancy and externalizing behavior problems in children. Neurotoxicology. 2013 ;34:167-74.

Llanos MN, Ronco AM. Fetal growth restriction is related to placental levels of cadmium, lead and arsenic but not with antioxidant activities. Reprod Toxicol. 2009 ;27(1):88-92.

Mahalingaiah S, Meeker JD, Pearson KR, et al. Temporal variability and predictors of urinary bisphenol A concentrations in men and women. Environ Health Perspect. 2008;116(2):173-8.

Masemola ML, van der Merwe L, Lombard Z, Viljoen D, Ramsay M. Reduced DNA methylation at the PEG3 DMR and KvDMR1 loci in children exposed to alcohol in utero: a South African Fetal Alcohol Syndrome cohort study. Front Genet. 2015 ;6:85.

Murphy SK , Huang Z, Hoyo C. Differentially methylated regions of imprinted genes in prenatal, perinatal and postnatal human tissues. PLoS One. 2012;7(7):e40924.

Nishijo M, Tawara K, Honda R, Nakagawa H, Tanebe K, Saito S. Relationship between newborn size and mother''s blood cadmium levels, Toyama, Japan. Arch Environ Health. 2004 ;59(1):22-5.

Ng S, Lin CC, Hwang YH, Hsieh WS, Liao HF, Chen PC. Mercury, APOE, and children''s neurodevelopment. Neurotoxicology. 2013 ;37:85-92.

Ng S, Lin CC, Jeng SF, Hwang YH, Hsieh WS, Chen PC. Mercury, APOE, and child behavior. Chemosphere. 2015 ;120:123-30.

Nye MD, Hoyo C, Murphy SK. In vitro lead exposure changes DNA methylation and expression of IGF2 and PEG1/MEST. Toxicol In Vitro. 2015;29(3):544-550.

Ode A, Källén K, Gustafsson P, et al. Fetal exposure to perfluorinated compounds and attention deficit hyperactivity disorder in childhood. PLoS One. 2014;9(4):e95891.

Olsen GW, Burris JM, Ehresman DJ, et al. Half-life of serum elimination of perfluorooctanesulfonate,perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ Health Perspect. 2007;115(9):1298-305.

Otsuka S, Maegawa S, Takamura A, Aberrant promoter methylation and expression of the imprinted PEG3 gene in glioma. Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(4):157-65.

Perera F, Li TY, Lin C, Tang D. Effects of prenatal polycyclic aromatic hydrocarbon exposure and environmental tobacco smoke on child IQ in a Chinese cohort. Environ Res. 2012 ;114:40-6.

Piedrahita JA. The role of imprinted genes in fetal growth abnormalities. Birth Defects Res A Clin Mol Teratol. 2011 ;91(8):682-92.

Rauh VA, Whyatt RM, Garfinkel R, et al. Developmental effects of exposure to environmental tobacco smoke and material hardship among inner-city children. Neurotoxicol Teratol. 2004 ;26(3):373-85.

Rauh V, Arunajadai S, Horton M, et al. Seven-year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide. Environ Health Perspect. 2011;119(8):1196-201.

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

Ronaghi M. Pyrosequencing sheds light on DNA sequencing. Genome Res. 2001;11(1):3-11.

Ryu HW, Lee DH, Won HR, et al. Influence of toxicologically relevant metals on human epigenetic regulation. Toxicol Res. 2015 ;31(1):1-9

Smeester L, Yosim AE, Nye MD, Hoyo C, Murphy SK, Fry RC. Imprinted genes and the environment: links to the toxic metals arsenic, cadmium, lead and mercury. Genes (Basel). 2014 ;5(2):477-96.

Swan SH. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environ Res. 2008 ;108(2):177-84.

Swan SH, Sathyanarayana S, Barrett ES, et al. First trimester phthalate exposure and anogenital distance in newborns. Hum Reprod. 2015 ;30(4):963-72.

Spence JE, Perciaccante RG, Greig GM, et al. Uniparental disomy as a mechanism for human genetic disease. Am J Hum Genet. 1988 ;42(2):217-26.

Stahl T, Mattern D, Brunn, H. Toxicology of perfluorinated compounds. Environmental Sciences Europe. 2011, 23:38

Takeuchi T, Tsutsumi O. Serum bisphenol a concentrations showed gender differences, possibly linked to androgen levels. Biochem Biophys Res Commun. 2002 ;291(1):76-8.

Takeuchi T, Tsutsumi O, Ikezuki Y, Takai Y, Taketani Y. Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and womenwith ovarian dysfunction. Endocr J. 2004 ;51(2):165-9.

Tanaka T. Reproductive and neurobehavioural toxicity study of bis(2-ethylhexyl) phthalate (DEHP) administered to mice in the diet. Food Chem Toxicol.2002;40:1499–1506.

Tanaka T. Effects of bis(2-ethylhexyl) phthalate (DEHP) on secondary sex ratio of mice in a cross-mating study. Food Chem Toxicol. 2003 ;41:1429–1432.

Tanaka T. Reproductive and neurobehavioural effects of bis(2-ethylhexyl) phthalate (DEHP) in a cross-mating toxicity study of mice. Food Chem Toxicol. 2005 ; 43:581–589.

Tian LL, Zhao YC, Wang XC, et al. Effects of gestational cadmium exposure on pregnancy outcome and development in the offspring at age 4.5 years. Biol Trace Elem Res. 2009 ;132(1-3):51-9.

Ungerer M, Knezovich J, Ramsay M. In utero alcohol exposure, epigenetic changes, and their consequences. Alcohol Res. 2013;35(1):37-46.

Vahter M. Effects of arsenic on maternal and fetal health. Annu Rev Nutr. 2009;29:381-99.

Valvi D, Casas M, Mendez MA, et al. Prenatal bisphenol A urine concentrations and early rapid growth and overweight risk in the offspring. Epidemiology. 2013 ;24(6):791-9.

Volkel W, Colnot T, Csanady G.A., Filser JG., Dekant W. Metabolism and kinetics of bisphenol A in humans at low doses following oral administration. Chem Res Toxicol. 2002; 15(10):1281–1287.

Vidal AC, Benjamin Neelon SE, Liu Y, et al. Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans. Genet Epigenet. 2014 ;6:37-44.

Washino N, Saijo Y, Sasaki S, et al. Correlations between prenatal exposure to perfluorinated chemicals and reduced fetal growth. Environ Health Perspect. 2009 ;117(4):660-7.

Watkins DJ, Wellenius GA, Butler RA, et al. Associations between serum perfluoroalkyl acids and LINE-1 DNA methylation. Environ Int. 2014 ;63:71-6.

Wilhelm-Benartzi CS, Houseman EA, Maccani MA, et al. In utero exposures, infant growth, and DNA methylation of repetitive elements and developmentally related genes in human placenta. Environ Health Perspect. 2012 ;120(2):296-302.

Wolff MS, Engel SM, Berkowitz GS, et al. Prenatal phenol and phthalate exposures and birth outcomes. Environ Health Perspect. 2008 ;116(8):1092-7.

Woodfine K, Huddleston JE, Murrell A. Quantitative analysis of DNA methylation at all human imprinted regions reveals preservation of epigenetic stability in adult somatic tissue. Epigenetics Chromatin. 2011 ;4(1):1.

Wu J, Ying T, Shen Z, Wang H. Effect of low-level prenatal mercury exposure on neonate neurobehavioral development in China. Pediatr Neurol. 2014 ;51(1):93-9.

Xie X, Ding G, Cui C, et al. The effects of low-level prenatal lead exposure on birth outcomes. Environ Pollut. 2013 ;175:30-4.

Xin Z , Soejima H, Higashimoto K, et al. A novel imprinted gene, KCNQ1DN, within the WT2 critical region of human chromosome 11p15.5 and its reduced expression in Wilms’ timors. J Biochem. 2000 ;128(5):847-53.

Yu XD, Zhang J, Yan CH, Shen XM. Prenatal exposure to manganese at environment relevant level and neonatal neurobehavioral development. Environ Res. 2014 Aug;133:232-8.


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