Present views on molecular mechanisms of formation of fetal growth restriction

Khachatryan Z.V., Kan N.E., Makarova N.P.

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow
The authors carried out a systematic analysis of the data given in the modern scientific literature on the molecular mechanisms of the formation of fetal growth restriction and their significance in obstetrics. The intrauterine environment can potentially affect biological activity in the fetus and lead to impaired growth and the development of long-term complications. The mechanisms underlying placental insufficiency, JAK-STAT signaling pathway, and the growth hormone-insulin-like growth factor-1 axis are considered. The paper gives data on the epigenetic regulation of these mechanisms and the importance of their further study in order to elaborate new therapeutic approaches in the future.

Keywords

fetal growth restriction
necroptosis
heat shock proteins
leptin
insulin-like growth factor-1
epigenetics

References

  1. Mifsud W., Sebire N.J. Placental pathology in early‐onset and late‐onset fetal growth restriction. Fetal Diagn. Ther. 2014; 36(2): 117-28. doi: 10.1159/000359969.
  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. 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.
  4. Стрижаков А.Н., Игнатко И.В., Байбулатова Ш.Ш., Богомазова И.М. Антенатальное метаболическое и эндокринное программирование при беременности высокого риска. Акушерство и гинекология. 2016; 10: 39-47. [Strizhakov A.N., Ignatko I.V., Baibulatova Sh.Sh., Bogomazova I.M. Antenatal metabolic and endocrine programming for high-risk pregnancy. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2016; (10): 39-47. (in Russian)].
  5. Devaskar S.U., Chu A. Intrauterine growth restriction: hungry for an answer. Physiology (Bethesda). 2016; 31(2): 131-46. http://dx.doi.org/10.1152/physiol.00033.2015
  6. Ananth C.V., Lavery J.A., Vintzileos A.M., Skupski D.W., Varner M., Saade G. et al. Severe placental abruption: clinical definition and associations with maternal complications. Am. J. Obstet. Gynecol. 2016; 214(2): 272. e1-272. e9. doi: 10.1016/j.ajog.2015.09.069.
  7. Huppertz B., Kadyrov M., Kingdom J.C. Apoptosis and its role in the trophoblast. Am. J. Obstet. Gynecol. 2006; 195(1): 29-39. DOI: 10.1371/journal.pone.0064351
  8. Sibley C.P. Treating the dysfunctional placenta. J. Endocrinol. 2017; 234(2): R81-97. https://doi.org/10.1186/s12958-019-0494-7
  9. Conrad M., Angeli J.P., Vandenabeele P., Stockwell B.R. Regulated necrosis: disease relevance and therapeutic opportunities. Nat. Rev. Drug Discov. 2016; 15(5): 348-66. http://dx.doi.org/10.1038/nrd.2015.6
  10. Narayan N., Lee I.H., Borenstein R., Sun J., Wang R., Tong G. et al. The NAD4 dependent deacetylase SIRT2 is required for programmed necrosis. Nature. 2012; 492(7428): 199-204. doi: 10.1038/nature11700.
  11. Silke J., Rickard J.A., Gerlic M. The diverse role of RIP kinases in necroptosis and inflammation. Nat. Immunol. 2015; 16(7): 689-97. doi: 10.1038/ni.3206.
  12. Chen X., Li W., Ren J., Huang D., He W.T., Song Y. et al. Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death. Cell Res. 2014; 24(1): 105-21. http://dx.doi.org/10.1038/cr.2013.171
  13. Polykratis A., Hermance N., Zelic M., Roderick J., Kim C., Van T.M. et al. Cutting edge: RIPK1 Kinase inactive mice are viable and protected from TNF-induced necroptosis in vivo. J. Immunol. 2014; 193(4): 1539-43. doi: 10.4049/jimmunol.1400590.
  14. Hannan N.J., Beard S., Binder N.K., Onda K., Kaitu’u-Lino T.J., Chen Q. et al. Key players of the necroptosis pathway RIPK1 and SIRT2 are altered in placenta from preeclampsia and fetal growth restriction. Placenta. 2017; 51: 1-9. doi: 10.1016/j.placenta.2017.01.002
  15. Bahr B., Galan H.L., Arroyo J.A. Decreased expression of phosphorylated placental heatshock protein 27 in human and ovine intrauterine growth restriction (IUGR). Placenta. 2014; 35(6): 404-10. doi: 10.1016/j.placenta.2014.03.001
  16. Clerico E.M., Meng W., Pozhidaeva A., Bhasne K., Petridis C., Gierasch L.M. Hsp70 molecular chaperones: multifunctional allosteric holding and unfolding machines. Biochem. J. 2019; 476(11): 1653-77. doi: 10.1042/BCJ20170380.
  17. Li W., Zhong X., Zhang L., Wang Y., Wang T. Heat shock protein 70 expression is increased in the liver of neonatal intrauterine growth retardation piglet. Asian-Australas. J. Anim. Sci. 2012; 25(8): 1096-101. https://doi.org/10.1007/s12192-012-0326-6
  18. Huang B.P., Lin C.S., Wang C.J., Kao S.H. Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2. Int. J. Med. Sci. 2017; 14(3): 284-93. DOI: 10.7150/ijms.17861
  19. Zhong X., Wang T., Zhang X., Li W. Heat shock protein 70 is upregulated in the intestine of intrauterine growth retardation piglets. Cell Stress Chaperones. 2010; 15(3): 335-42. doi: 10.1007/s12192-009-0148-3
  20. Varvarigou A.A. Intrauterine growth restriction as a potential risk factor for disease onset in adulthood. J. Pediatr. Endocrinol. Metab. 2010; 23(3): 215-24. DOI: 10.1515/JPEM.2010.23.3.215
  21. Dodington D.W., Desai H.R., Woo M. JAK/STAT – emerging players in metabolism. Trends Endocrinol. Metab. 2018; 29(1): 55-65. DOI: 10.1016/j.tem.2017.11.001
  22. Tzschoppe A., Struwe E., Rascher W., Dörr H.G., Schild R.L., Goecke T.W. et al. Intrauterine growth restriction (IUGR) is associated with increased leptin synthesis and binding capability in neonates. Clin. Endocrinol. (Oxf.). 2011; 74(4): 459-66. doi: 10.1111/j.1365-2265.2010.03943.x.
  23. Mullen M., Gonzalez-Perez R.R. Leptin-induced JAK/STAT signaling and cancer growth. Vaccines (Basel). 2016; 4(3): 26. Article (PDF Available) in Vaccines 4(3):26 · July 2016 with 60 Reads DOI: 10.3390/vaccines4030026
  24. Yi Y., Cheng J.C., Klausen C., Leung P.C.K. TGF-β1 inhibits human trophoblast cell invasion by upregulating cyclooxygenase-2. Placenta. 2018; 68: 44-51. doi: 10.1016/j.placenta.2018.06.313.
  25. Chauvin S., Yinon Y., Xu J., Ermini L., Sallais J., Tagliaferro A. et al. Aberrant TGFβ signalling contributes to dysregulation of sphingolipid metabolism in intrauterine growth restriction. J. Clin. Endocrinol. Metab. 2015; 100(7): E986-96. doi: 10.1210/jc.2015-1288
  26. Vähätalo R., Asikainen T.M., Karikoski R., Kinnula V.L., White C.W., Andersson S.,et al. Expression of transcription factor GATA-6 in alveolar epithelial cells is linked to neonatal lung disease. Neonatology. 2011; 99(3): 231-40. doi: 10.1159/000317827
  27. Alcázar M.A., Dinger K., Rother E., Östreicher I., Vohlen C., Plank C. et al. Prevention of early postnatal hyperalimentation protects against activation of transforming growth factor-β/bone morphogenetic protein and interleukin-6 signaling in rat lungs after intrauterine growth restriction. J. Nutr. 2014; 144(12): 1943-51. doi: 10.3945/jn.114.197657
  28. Martín-Estal I., de la Garza R. G., Castilla-Cortázar I. Intrauterine growth retardation (IUGR) as a novel condition of insulin-like growth factor-1 (IGF-1)deficiency. Rev. Physiol. Biochem. Pharmacol. 2016; 170: 1-35.DOI: 10.1007/112_2016_1
  29. Sferruzzi-Perri A.N., Owens J.A., Pringle K.G., Roberts C.T. The neglected role of insulin-like growth factors in the maternal circulation regulating fetal growth. J. Physiol. 2011; 589(Pt 1): 7-20. doi: 10.1113/jphysiol.2010.198622.
  30. Baumann M.U., Schneider H., Malek A., Palta V., Surbek D.V., Sager R. et al. Regulation of human trophoblast GLUT1 glucose transporter by insulin-like growth factor I (IGF-I). PLoS One. 2014; 9(8): e106037. doi: 10.1371/journal.pone.0106037
  31. Illingworth R.S., Gruenewald-Schneider U., Webb S., Kerr A.R., James K.D., Turner D.J. et al. Orphan CpG islands identify numerous conserved promoters in the mammalian genome. PLoS Genet. 2010; 6(9): e1001134. doi: 10.1371/journal.pgen.1001134.
  32. Jang H.S., Shin W.J., Lee J.E., Do J.T. CpG and Non-CpG methylation in epigenetic gene regulation and brain function. Genes (Basel). 2017; 8(6): 148. doi: 10.3390/genes8060148.
  33. Ye J., Wu W., Li Y., Li L. Influences of the gut microbiota on DNA methylation and histone modification. Dig. Dis. Sci. 2017; 62(5): 1155-64. doi: 10.1007/s10620-017-4538-6.
  34. Sen P., Shah P.P., Nativio R., Berger S.L. Epigenetic mechanisms of longevity and aging. Cell. 2016; 166(4): 822-39. https://doi.org/10.1186/s13148-017-0365-z
  35. O’Brien J., Hayder H., Zayed Y., Peng C. Overview of MicroRNA biogenesis, mechanisms of actions, and circulation. Front. Endocrinol. (Lausanne). 2018; 9: 402. DOI: 10.3389/fendo.2018.00402
  36. Rotwein P. Diversification of the insulin-like growth factor 1 gene in mammals. PLoS One. 2017; 12(12): e0189642. DOI: 10.1371/journal.pone.0189642
  37. Chia D.J., Varco-Merth B., Rotwein P. Dispersed chromosomal Stat5b-binding elements mediate growth hormone-activated insulin-like growth factor-I gene transcription. J. Biol. Chem. 2010; 285(23): 17636-47. doi: 10.1074/jbc.M110.117697
  38. Rotwein P. Mapping the growth hormone–Stat5b–IGF-I transcriptional circuit. Trends Endocrinol. Metab. 2012; 23(4): 186-93. doi: 10.1016/j.tem.2012.01.001.
  39. Klammt J., Neumann D., Gevers E.F., Andrew S.F., Schwartz I.D., Rockstroh D. et al. Dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation. Nat. Commun. 2018; 9(1): 2105. doi: 10.1038/s41467-018-04521-0.
  40. Zhou Z., Liu Y.T., Ma L., Gong T., Hu Y.N., Li H.T. et al. Independent manipulation of histone H3 modifications in individual nucleosomes reveals the contributions of sister histones to transcription. Elife. 2017; 6: e30178. https://doi.org/10.1007/s00294-018-0910-0
  41. Chantalat S., Depaux A., Héry P., Barral S., Thuret J.Y., Dimitrov S. et al. Histone H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin. Genome Res. 2011; 21(9): 1426-37. doi: 10.1101/gr.118091.110.
  42. Fu Q., McKnight R.A., Callaway C.W., Yu X., Lane R.H., Majnik A.V. Intrauterine growth restriction disrupts developmental epigenetics around distal growth hormone response elements on the rat hepatic IGF-1 gene. FASEB J. 2015; 29(4): 1176-84. DOI: 10.1096/fj.14-258442
  43. 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. [Degtyareva E.I., Grigoryan O.R., Volevodz N.N., Andreeva E.N., Klimenchenko N.I., Melnichenko G.A., Dedov I.I., Sukhikh G.T. Role of gene imprinting in intrauterine growth restriction. Akusherstvo i ginekologiya/Obstetrics and Gynecology. 2015; (12): 5-10. (in Russian)].

Received 20.06.2109

Accepted 21.06.2019

About the Authors

Zarine V. Khachatryan, postgraduate student of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov Ministry of Health of Russia (117997, Moscow, Ac. Oparina, 4 str. Tel.: +7-909-656-24-56. E-mail: z.v.khachatryan@gmail.com
Natalia E. Kan, PhD, MD, professor of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov Ministry of Health of Russia (117997, Moscow, Ac. Oparina, 4 str.). Tel.: +7-926-220-86-55. E-mail: kan-med@mail.ru. Number Researcher ID B-2370-2015.
ORCID ID 0000-0001-5087-5946
Natalia P. Makarova, Doctor of Biological Sciences, leading researcher of IVF Department of the National Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov Ministry of Health of Russia (117997, Moscow, Ac. Oparina, 4 str.). Tel.: 8 (495) 438-77-00 E-mail: np_makarova@oparina4.ru

For citation: Khachatryan Z.V., Kan N.E., Makarova N.P. Present views on molecular mechanisms of formation of fetal growth restriction.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2019; (10): 22-26. (in Russian).
https://dx.doi.org/10.18565/aig.2019.10.22-26

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