Gene methylation in the placenta of fetuses with fetal growth restriction


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Objective. To study a DNA methylation profile in the placenta in fetuses with fetal growth restriction. Subjects and methods. Thirty-eight placental samples, obtained from patients after spontaneous and surgical delivery, were investigated during the study. The women were divided into 2groups: 1) 18 patients with a confirmed diagnosis of fetal growth restriction; 2) 20 patients with physiological pregnancy. DNA was isolated from tissues using K-sorb columns (Synthol, Russia). Then bisulfite conversion and polymerase chain reaction with primers to an island methylation fragment of the studied genes were carried out. The methylation level was determined by methylation-specific high resolution melting curve analysis using Precision Melt Analysis Software (BioRad, USA). Results. The relative level of methylation of the TLR2 gene in the placentas in the presence of fetal growth restriction was found to be significantly lower than that in the physiological pregnancy group (p = 0.01). The study of methylation of the IGF2/H19 imprinting control region (ICR) also showed a significant decrease in the relative level of methylation in the placentas in fetal growth restriction compared with the comparison group (p <0.001). Conclusion. The findings indicate that methylation of the TLR2 gene and the IGF2/H19 ICR play a role in fetal growth restriction and that further investigations of the levels of methylation of these genes in other biological substrates are promising in developing new diagnostic techniques.

Full Text

Restricted Access

About the authors

Zarine V. Khachatryan

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: z.v.khachatryan@gmail.com

Natalia E. Kan

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: kan-med@mail.ru

Aleksey M. Krasnyi

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia; N.K. Koltsov Institute of Developmental Biology, Russian Academy of Sciences

Email: alexred@list.ru

Alsu A. Sadekova

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: a_sadekova@oparina4.ru

Sergey V. Kurevlev

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: s_kurevlev@oparina4.ru

Victor L. Tyutyunnik

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: tioutiounnik@mail.ru

References

  1. Barker D.J.P, Osmond C. Infant mortality, childhood nutrition, and ischaemic heartdisease in England and Wales. Lancet. 1986; 10, 1(8489): 1077-81. doi: 10.1016/s0140-6736(86)91340-1
  2. Kwon E.J., Kim Y.J. What is fetal programming: a lifetime health is under the control of in utero health. Obstet Gynecol Sci. 2017; 60(6): 506-19. doi: 10.5468/ogs.2017.60.6.506
  3. Hales C.N., Barker D.J.P. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Int J Epidemiol. 2013; 42(5): 1215-22 doi: 10.1093/ije/dyt133
  4. Дегтярева Е.И., Григорян О.Р., Волеводз Н.Н., Андреева Е.Н., Клименченко Н.И., Мельниченко Г.А., Дедов И.И., Сухих Г.Т. Роль импринтинга генов при внутриутробной задержке роста плода. Акушерство и гинекология. 2015; 12: 5-10.
  5. Marciniak A., Patro-Maiysza J., Kimber-Trojnar Z., Marciniak B., Oleszczuk J., Leszczynska-Gorzelak B. Fetal programming of the metabolic syndrome. Taiwan J Obstet Gynecol. 2017; 56(2):133-8. doi: 10.1016/j.tjog.2017.01.001
  6. Menendez-Castro C., Rascher W., Hartner A. Intrauterine growth restriction -impact on cardiovascular diseases later in life. Mol Cell Pediatr. 2018; 5(1): 4. doi: 10.1186/s40348-018-0082-5
  7. Faa G., Manchia M., Pintus R., Gerosa C., Marcialis M.A., Fanos V. Fetal programming of neuropsychiatric disorders. Birth Defects Res C Embryo Today. 2016; 108(3): 207-223. doi: 10.1002/ bdrc.21139
  8. Feil R., Fraga M.F. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet. 2012;13(2): 97-109. doi: 10.1038/ nrg3142.
  9. Manolio T. A., Collins F.S., Cox N.J., Goldstein D.B., Hindorff L.A., Hunter D.J. et al. Finding the missing heritability of complex diseases.Nature. 2009; 461(7265): 747-53. doi: 10.1038/nature08494
  10. Salam R.A., Das J.K., Bhutta Z.A. Impact of intrauterine growth restriction on long-term health. Curr Opin Clin Nutr Metab Care. 2014;17(3): 249-54. doi: 10.1097/Mm.0000000000000051
  11. Chen P.Y., Ganguly A., Rubbi L., Orozco L.D., Morselli M., Ashraf D., et al. Intrauterine calorie restriction affects placental DNA methylation and gene expression. Physiol Genomics. 2013; 45(14): 565-76. doi: 10.1152/ physiolgenomics.00034.2013
  12. Banister C.E., Koestler D.C., Maccani M.A., Padbury J.F., Houseman E.A., Marsit C.J. Infant growth restriction is associated with distinct patterns of DNA methylation in human placentas. Epigenetics. 2011; 6(7): 920-7. doi: 10.4161/ epi.6.7.16079
  13. Vaiman D. Genes, epigenetics and miRNA regulation in the placenta. Placenta. 2017; 52:127-33. doi: 10.1016/j.placenta.2016.12.026
  14. Marsit C.J. Placental epigenetics in children’s environmental health. Semin Reprod Med. 2016; 34(1): 36-41. doi: 10.1055/s-0035-1570028
  15. Lillycrop K.A., Burdge G.C. Environmental challenge, epigenetic plasticity and the induction of altered phenotypes in mammals. Epigenomics. 2014; 6(6): 623-36. doi: 10.2217/epi.14.51
  16. Nelissen E.C.M., van Montfoort A.P., Dumoulin J.C., Evers J.L. Epigenetics and the placenta. Hum Reprod Update. 2011;17(3): 397-417. doi: 10.1093/ humupd/dmq052
  17. Moore L.D., Le T., Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013; 38(1): 23-38. doi: 10.1038/npp.2012.112
  18. Wojdacz T.K., Dobrovic A., Hansen L.L. Methylation-sensitive high-resolution melting. Nat Protoc. 2008 3(12):1903-8. doi: 10.1093/nar/ gkm013
  19. Красный А.М., Садекова А.А., Волгина Н.Е., Машаева Р.И., Кометова В.В., Хабас Г.Н., Голицына Ю.С., Носова Ю.В., Оводенко Д.Л. Исследование уровня метилирования гена RASSF1 в плазме и опухоли при раке эндометрия. Бюллетень экспериментальной биологии и медицины. 2019; 2: 223-7
  20. Ma Y., Krikun G., Abrahams V.M., Mor G., Guiler S. Cell type-specific expression and function of toll-like receptors 2 and 4 in human placenta: implications in fetal infection. Placenta. 2007; 28(10): 1024-31. doi: 10.1016/j. placenta.2007.05.003
  21. Erboga M., Kanter M. Trophoblast cell proliferation and apoptosis in placental development during early gestation period in rats. Anal Quant Cytopathol Histpathol. 2015; 37(5): 286-94.
  22. Koga K., Aldo P.B., Mor G. Toll-like receptors and pregnancy: trophoblast as modulators of the immune response. J Obstet Gynaecol Res. 2009; 35(2): 191-202. doi: 10.1111/j.1447-0756.2008.00963.x
  23. Abrahams V.M., Bole-Aldo P., Kim Y.M., Straszewski-Chavez S.L., Chaiworapongsa T., Romero R., et al. Divergent trophoblast responses to bacterial products mediated by TLRs. J Immunol. 2004; 173(7): 4286-96. doi: 10.4049/ jimmunol.173.7.4286
  24. Silva J.F., Ocarino N.M., Serakides R. Spatiotemporal expression profile of proteases and immunological, angiogenic, hormonal and apoptotic mediators in rat placenta before and during intrauterine trophoblast migration. Reprod Fertil Dev. 2017; 29(9): 1774-86. doi: 10.1071/RD16280
  25. Tycko B. Imprinted genes in placental growth and obstetric disorders. Cytogenet Genome Res. 2006; 113(1-4): 271-8. doi: 10.1159/000090842
  26. John R.M. Imprinted genes and the regulation of placental endocrine function: Pregnancy and beyond. Placenta. 2017; 56: 86-90. doi: 10.1016/j. placenta.2017.01.099
  27. Christians J.K., Leavey K., Cox B.J. Associations between imprinted gene expression in the placenta, human fetal growth and preeclampsia. Biol Lett. 2017;13(11): pii: 20170643.doi: 10.1098/rsbl.2017.0643
  28. Bartholdi D., Krajewska-Walasek M., Ounap K., Gaspar H., Chrzanowska K.H., Ilyana H. et al. Epigenetic mutations of the imprinted IGF2-H19 domain in Silver-Russell syndrome (SRS): results from a large cohort of patients with SRS and SRS-like phenotypes. J Med Genet. 2009; 46(3): 192-7. doi: 10.1136/jmg.2008.061820
  29. Du M., Zhou W, Beatty L.G., Weksberg R., Sadowski P.D., et al. The KCNQ1OT1 promoter, a key regulator of genomic imprinting in human chromosome 11p15. 5. Genomics. 2004; 84(2): 288-300. doi: 10.1016/j.ygeno.2004.03.008
  30. Koukoura O., Sifakis S., Soufla G., Zaravinos A., Apostolidou S., Jones A., et al. Loss of imprinting and aberrant methylation of IGF2 in placentas from pregnancies complicated with fetal growth restriction. Int J Mol Med. 2011; 28(4): 481-7. doi: 10.3892/ijmm.2011.754.
  31. Tabano S., Colapietro P., Cetin I., Grati F.R., Zanutto S., Mandd C., Antonazzo P. et al. Epigenetic modulation of the IGF2/H19 imprinted domain in human embryonic and extra-embryonic compartments and its possible role in fetal growth restriction. Epigenetics. 2010; 5(4): 313-24. doi: 10.4161/epi.5.4.11637
  32. Xiao X., Zhao Y., Jin R., Chen J., Wang X., et al. Fetal growth restriction and methylation of growth-related genes in the placenta. Epigenomics. 2016; 8(1): 33-42. doi: 10.2217/epi.15.101.
  33. St-Pierre J., Hivert M.F., Perron P., Poirier P., Guay S.P, Brisson D., et al. IGF2 DNA methylation is a modulator of newborn’s fetal growth and development. Epigenetics. 2012; 7(10): 1125-32. doi: 10.4161/epi.21855.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2019 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies