Lower S-adenosylmethionine levels and DNA hypomethylation of placental growth factor (PlGF) in placental tissue of early-onset preeclampsia-complicated pregnancies
Autoři:
Sandra G. Heil aff001; Emilie M. Herzog aff002; Pieter H. Griffioen aff001; Bertrand van Zelst aff001; Sten P. Willemsen aff002; Yolanda B. de Rijke aff001; Regine P. M. Steegers-Theunissen aff002; Eric A. P. Steegers aff002
Působiště autorů:
Erasmus MC University Medical Center, Rotterdam, The Netherlands, Department of Clinical Chemistry
aff001; Erasmus MC University Medical Center, Rotterdam, The Netherlands, Department of Obstetrics and Gynaecology
aff002; Erasmus MC University Medical Center, Rotterdam, The Netherlands, Department of Biostatistics
aff003
Vyšlo v časopise:
PLoS ONE 14(12)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0226969
Souhrn
Introduction
The pathophysiology of preeclampsia is largely unknown. Serum placental induced growth factor (PlGF) levels are decreased during second trimester pregnancy. Aberrant DNA methylation is suggested to be involved in the etiology of preeclampsia (PE). We hypothesize that DNA methylation is altered in PE placentas determined the methylation index by measuring placental S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) levels. In addition, we assessed global DNA methylation status by long-interspersed nuclear element-1 (LINE-1) and DNA methylation status of the PlGF gene.
Methods
Placental tissue of 11 early onset PE (EOPE), 11 late onset PE (LOPE) and 60 controls consisting of 25 uncomplicated controls 20 fetal growth restriction (FGR) and 15 preterm births (PTB) controls was collected from a nested case-control study of The Rotterdam Periconceptional Cohort. RNA and DNA was isolated from placental tissue and DNA was treated with sodium bisulfite. SAM and SAH levels were measured by LC-ESI-MS/MS. Methylation of LINE-1 and PlGF genes was analyzed by Sequenom Epityper and. mRNA expression of PlGF was assessed with qPCR. Differences were assessed by analysis of covariance (ANCOVA) corrected for gestational age and birth weight.
Results
Placental SAM levels were significantly lower in placental tissue of EOPE pregnancies compared to PTB controls (mean difference -240 ± 71.4 nmol/g protein, P = 0.01). PlGF DNA methylation was decreased in placental tissue of EOPE cases versus LOPE (mean difference -17.4 ± 5.1%, P = 0.01), uncomplicated controls (mean difference -23.4 ± 5.4%%, P <0.001), FGR controls (mean difference -17.9 ± 4.6%, P = 0.002) and PTB controls (mean difference -11.3 ± 3.8% P = 0.04). No significant differences were observed in SAH, SAM:SAH ratio, LINE-1 DNA methylation and PlGF mRNA expression between groups.
Discussion
The hypomethylation state of the placenta in EOPE, which is reflected by lower SAM and PlGF DNA hypomethylation underlines the possible role of placental DNA hypomethylation in the pathophysiology of EOPE, which needs further investigation.
Klíčová slova:
Birth weight – DNA methylation – Hypertensive disorders in pregnancy – Methylation – placenta – Pregnancy – Preterm birth
Zdroje
1. Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010;376(9741):631–44. Epub 2010/07/06. doi: 10.1016/S0140-6736(10)60279-6 20598363.
2. Brosens IA, Robertson WB, Dixon HG. The role of the spiral arteries in the pathogenesis of preeclampsia. Obstet Gynecol Annu. 1972;1:177–91. Epub 1972/01/01. 4669123.
3. Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am J Obstet Gynecol. 2013;209(6):544.e1–e12. Epub 2013/08/27. doi: 10.1016/j.ajog.2013.08.019 23973398.
4. Zusterzeel PL, Visser W, Blom HJ, Peters WH, Heil SG, Steegers EA. Methylenetetrahydrofolate reductase polymorphisms in preeclampsia and the HELLP syndrome. Hypertens Pregnancy. 2000;19(3):299–307. Epub 2000/12/19. doi: 10.1081/prg-100101991 11118403.
5. Bergen NE, Jaddoe VW, Timmermans S, Hofman A, Lindemans J, Russcher H, et al. Homocysteine and folate concentrations in early pregnancy and the risk of adverse pregnancy outcomes: the Generation R Study. Bjog. 2012;119(6):739–51. Epub 2012/04/12. doi: 10.1111/j.1471-0528.2012.03321.x 22489763.
6. van Mil NH, Bouwland-Both MI, Stolk L, Verbiest MM, Hofman A, Jaddoe VW, et al. Determinants of maternal pregnancy one-carbon metabolism and newborn human DNA methylation profiles. Reproduction. 2014;148(6):581–92. Epub 2014/11/14. doi: 10.1530/REP-14-0260 25392189.
7. Steegers-Theunissen RP, Twigt J, Pestinger V, Sinclair KD. The periconceptional period, reproduction and long-term health of offspring: the importance of one-carbon metabolism. Hum Reprod Update. 2013. Epub 2013/08/21. doi: 10.1093/humupd/dmt041 23959022.
8. Castro R, Rivera I, Struys EA, Jansen EE, Ravasco P, Camilo ME, et al. Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease. Clin Chem. 2003;49(8):1292–6. Epub 2003/07/26. doi: 10.1373/49.8.1292 12881445.
9. Ingrosso D, Cimmino A, Perna AF, Masella L, De Santo NG, De Bonis ML, et al. Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia. Lancet. 2003;361(9370):1693–9. Epub 2003/05/28. doi: 10.1016/S0140-6736(03)13372-7 12767735.
10. Mandaviya PR, Stolk L, Heil SG. Homocysteine and DNA methylation: a review of animal and human literature. Mol Genet Metab. 2014;113(4):243–52. Epub 2014/12/03. doi: 10.1016/j.ymgme.2014.10.006 25456744.
11. Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111(5):649–58. Epub 2003/03/06. doi: 10.1172/JCI17189 12618519.
12. Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672–83. doi: 10.1056/NEJMoa031884 14764923.
13. Karumanchi SA, Maynard SE, Stillman IE, Epstein FH, Sukhatme VP. Preeclampsia: a renal perspective. Kidney Int. 2005;67(6):2101–13. Epub 2005/05/11. doi: 10.1111/j.1523-1755.2005.00316.x 15882253.
14. Bouwland-Both MI, Steegers EA, Lindemans J, Russcher H, Hofman A, Geurts-Moespot AJ, et al. Maternal soluble fms-like tyrosine kinase-1, placental growth factor, plasminogen activator inhibitor-2, and folate concentrations and early fetal size: the Generation R study. Am J Obstet Gynecol. 2013;209(2):121.e1–11. Epub 2013/04/16. doi: 10.1016/j.ajog.2013.04.009 23583216.
15. Coolman M, Timmermans S, de Groot CJ, Russcher H, Lindemans J, Hofman A, et al. Angiogenic and fibrinolytic factors in blood during the first half of pregnancy and adverse pregnancy outcomes. Obstet Gynecol. 2012;119(6):1190–200. Epub 2012/05/24. doi: 10.1097/AOG.0b013e318256187f 22617584.
16. Steegers-Theunissen RP, Verheijden-Paulissen JJ, van Uitert EM, Wildhagen MF, Exalto N, Koning AH, et al. Cohort Profile: The Rotterdam Periconceptional Cohort (Predict Study). Int J Epidemiol. 2015. Epub 2015/08/01. doi: 10.1093/ije/dyv147 26224071.
17. Herzog EM, Eggink AJ, van der Zee M, Lagendijk J, Willemsen SP, de Jonge R, et al. The impact of early- and late-onset preeclampsia on umbilical cord blood cell populations. J Reprod Immunol. 2016;116:81–5. Epub 2016/05/31. doi: 10.1016/j.jri.2016.05.002 27239988.
18. Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy. 2001;20(1):IX–XIV. Epub 2002/06/05. 12044323.
19. Visser GH, Eilers PH, Elferink-Stinkens PM, Merkus HM, Wit JM. New Dutch reference curves for birthweight by gestational age. Early Hum Dev. 2009;85(12):737–44. Epub 2009/11/17. doi: 10.1016/j.earlhumdev.2009.09.008 19914013.
20. Kok RM, Smith DE, Barto R, Spijkerman AM, Teerlink T, Gellekink HJ, et al. Global DNA methylation measured by liquid chromatography-tandem mass spectrometry: analytical technique, reference values and determinants in healthy subjects. Clin Chem Lab Med. 2007;45(7):903–11. Epub 2007/07/10. doi: 10.1515/CCLM.2007.137 17617036.
21. Wang L, Wang F, Guan J, Le J, Wu L, Zou J, et al. Relation between hypomethylation of long interspersed nucleotide elements and risk of neural tube defects. Am J Clin Nutr. 2010 doi: 10.3945/ajcn.2009.28858 20164316.
22. Kulkarni AV, Mehendale SS, Yadav HR, Joshi SR. Reduced placental docosahexaenoic acid levels associated with increased levels of sFlt-1 in preeclampsia. Prostaglandins Leukot Essent Fatty Acids. 2011;84(1–2):51–5. Epub 2010/10/20. doi: 10.1016/j.plefa.2010.09.005 20956072.
23. Nomura Y, Lambertini L, Rialdi A, Lee M, Mystal EY, Grabie M, et al. Global methylation in the placenta and umbilical cord blood from pregnancies with maternal gestational diabetes, preeclampsia, and obesity. Reprod Sci. 2014;21(1):131–7. Epub 2013/06/15. doi: 10.1177/1933719113492206 23765376.
24. Wilson SL, Blair JD, Hogg K, Langlois S, von Dadelszen P, Robinson WP. Placental DNA methylation at term reflects maternal serum levels of INHA and FN1, but not PAPPA, early in pregnancy. BMC Med Genet. 2015;16(1). doi: 10.1186/s12881-015-0257-z 26654447
25. Herzog EM, Eggink AJ, Willemsen SP, Slieker RC, Wijnands KPJ, Felix JF, et al. Early- and late-onset preeclampsia and the tissue-specific epigenome of the placenta and newborn. Placenta. 2017;58((Herzog E.M., e.herzog@erasmusmc.nl; Eggink A.J., a.eggink@erasmusmc.nl; Willemsen S.P., s.willemsen@erasmusmc.nl; Wijnands K.P.J., k.wijnands@erasmusmc.nl; Steegers-Theunissen R.P.M., r.steegers@erasmusmc.nl) Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands):122–32. doi: 10.1016/j.placenta.2017.08.070 28962690
26. Yan YH, Yi P, Zheng YR, Yu LL, Han J, Han XM, et al. Screening for preeclampsia pathogenesis related genes. Eur Rev Med Pharmacol Sci. 2013;17(22):3083–94. 24302191
27. Hogg K, Blair J, McFadden D, Dadelszen Pv, … Early onset pre-eclampsia is associated with altered DNA methylation of cortisol-signalling and steroidogenic genes in the placenta: journals.plos.org; 2013.
28. Blair JD, Yuen RK, Lim BK, McFadden DE, von Dadelszen P, Robinson WP. Widespread DNA hypomethylation at gene enhancer regions in placentas associated with early-onset pre-eclampsia. Mol Hum Reprod. 2013;19(10):697–708. Epub 2013/06/19. doi: 10.1093/molehr/gat044 23770704.
29. Martin E, Ray PD, Smeester L, Grace MR, Boggess K, Fry RC. Epigenetics and Preeclampsia: Defining Functional Epimutations in the Preeclamptic Placenta Related to the TGF-beta Pathway. PLoS ONE. 2015;10(10):e0141294. doi: 10.1371/journal.pone.0141294 26510177.
30. Gao WL, Li D, Xiao ZX, Liao QP, Yang HX, Li YX, et al. Detection of global DNA methylation and paternally imprinted H19 gene methylation in preeclamptic placentas. Hypertens Res. 2011;34(5):655–61. Epub 2011/02/18. doi: 10.1038/hr.2011.9 21326306.
31. Kulkarni A, Chavan-Gautam P, Mehendale S, Yadav H, Joshi S. Global DNA methylation patterns in placenta and its association with maternal hypertension in pre-eclampsia. DNA Cell Biol. 2011;30(2):79–84. Epub 2010/11/04. doi: 10.1089/dna.2010.1084 21043832.
32. Liu H, Tang Y, Liu X, Zhou Q, Xiao X, Lan F, et al. 14-3-3 tau (YWHAQ) gene promoter hypermethylation in human placenta of preeclampsia. Placenta. 2014;35(12):981–8. doi: 10.1016/j.placenta.2014.09.016 25305692
33. Bourque DK, Avila L, Peñaherrera M, von Dadelszen P, Robinson WP. Decreased Placental Methylation at the H19/IGF2 Imprinting Control Region is Associated with Normotensive Intrauterine Growth Restriction but not Preeclampsia. Placenta. 2010;31(3):197–202. doi: 10.1016/j.placenta.2009.12.003 20060582
34. Anton L, Brown AG, Bartolomei MS, Elovitz MA. Differential methylation of genes associated with cell adhesion in preeclamptic placentas. PLoS ONE. 2014;9(6). doi: 10.1371/journal.pone.0100148 24963923
35. Zhu L, Lv R, Kong L, Cheng H, Lan F, Li X. Genome-wide mapping of 5mC and 5hmC identified differentially modified genomic regions in late-onset severe preeclampsia: A pilot study. PLoS ONE. 2015;10(7). doi: 10.1371/journal.pone.0134119 26214307
36. Wikstrom AK, Larsson A, Eriksson UJ, Nash P, Norden-Lindeberg S, Olovsson M. Placental growth factor and soluble FMS-like tyrosine kinase-1 in early-onset and late-onset preeclampsia. Obstet Gynecol. 2007;109(6):1368–74. Epub 2007/06/02. doi: 10.1097/01.AOG.0000264552.85436.a1 17540809.
37. Chuah TT, Tey WS, Ng MJ, Tan ETH, Chern B, Tan KH. Serum sFlt-1/PlGF ratio has better diagnostic ability in early- compared to late-onset pre-eclampsia. J Perinat Med. 2018;47(1):35–40. Epub 2018/05/01. doi: 10.1515/jpm-2017-0288 29708884.
38. Hoeller A, Ehrlich L, Golic M, Herse F, Perschel FH, Siwetz M, et al. Placental expression of sFlt-1 and PlGF in early preeclampsia vs. early IUGR vs. age-matched healthy pregnancies. Hypertens Pregnancy. 2017;36(2):151–60. Epub 2017/06/14. doi: 10.1080/10641955.2016.1273363 28609172.
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