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Expression pattern of tumor necrosis factor alpha in placentae of idiopathic fetal growth restriction

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Abstract

Tumor Necrosis Factor-Alpha (TNF-α) is one of the proinflammatory cytokines that provokes a variety of biological effects on the placenta. The increased placental exposure to TNF-α have induced impaired fetal development in experimental animals, but no data are available on the expression and localization of TNF-α in human placenta of idiopathic fetal growth restriction (FGR). The aim of this study was to characterize the immunohistochemical expression and localization of TNF-α in idiopathic FGR placentae in comparison with those of appropriate for gestational age (AGA) fetuses. 75 human placentae were collected between April, 2010 and March, 2011; 50 placentae were collected from pregnancies associated with idiopathic FGR and 25 placentae from AGA pregnancies. Histological and Immunohistochemical methodologies were employed in formalin fixed paraffin-embedded sections from the placentae of all subjects. Area percent of TNF-α immunostaining was evaluated using image analysis technique. In both AGA and idiopathic FGR placentae, cytoplasmic TNF-α was localized in the decidual and chorionic trophoblasts and in the endothelium of decidual and chorionic vessels. Trophoblast giant cells (TGC) in the decidua and chorionic villi of AGA specimens show deficient or negative TNF-α immunoexpression while those of idiopathic FGR show positive immunostaining. The mean area percent of TNF-α staining was greater in idiopathic FGR placentae (5.93 ± 0.69) compared to AGA ones (3.28 ± 0.41) (p = 0.001). Enhanced placental expression and specific cellular localization and of TNF-α are expected to contribute to impaired fetal development in idiopathic FGR and the TGCs are proposed to be an obvious source of this cytokine in such cases.

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Abbreviations

TNF-α:

Tumor Necrosis Factor-Alpha

FGR:

Fetal growth restriction

AGA:

Appropriate for gestational age

TGC:

Trophoblast giant cells

References

  • Amarilyo G, Oren A, Mimouni FB, Ochshorn Y, Deutsch V, Mandel D (2011) Increased cord serum inflammatory markers in small-for-gestational-age neonates. J Perinatol 31(1):30–32

    Article  PubMed  CAS  Google Scholar 

  • Bancroft JD, Gamble M (2002) Theory and practice of histological techniques. Churchill Livingstone, London

    Google Scholar 

  • Bertucci MC, Loose JM, Wallace EM, Jenkin G, Miller SL (2011) Anti-inflammatory therapy in an ovine model of fetal hypoxia induced by single umbilical artery ligation. Reprod Fertil Dev 23(2):346–352

    Article  PubMed  CAS  Google Scholar 

  • Bevilacqua EM, Abrahamsohn PA (1988) Ultrastructure of trophoblast giant cell transformation during the invasive stage of implantation of the mouse embryo. J Morphol 198:341–351

    Article  PubMed  CAS  Google Scholar 

  • Bevilacqua MP, Pober JS, Majeau GR, Fiers W, Cotran RS, Gimbrone MA Jr (1986) Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium; characterization and comparison with the actions of interleukin-1. Proc Natl Acad Sci U S A 83(12):4533–4537

    Article  PubMed  CAS  Google Scholar 

  • Briana DD, Malamitsi-Puchner A (2009) Intrauterine growth restriction and adult disease: the role of adipocytokines. Eur J Endocrinol 160(3):337–347

    Article  PubMed  CAS  Google Scholar 

  • Campbell LR, Pang Y, Ojeda NB, Zheng B, Rhodes PG, Alexander BT (2012) Intracerebral lipopolysaccharide induces neuroinflammatory change and augmented brain injury in growth-restricted neonatal rats. Pediatr Res. doi:10.1038/pr.2012.26

    Google Scholar 

  • Conrad KP, Benyo DF (1997) Placental cytokines and the pathogenesis of preeclampsia. Am J Reprod Immunol 37:240–249

    Article  PubMed  CAS  Google Scholar 

  • Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Rouse DJ, Spong CY (2010) Disorders of amniotic fluid volume. In: Williams obstetrics, 23rd edn. McGraw-Hill Companies, New York, pp 490–499

  • Foltran F, Berchialla P, Bernasconi S, Grossi E, Gregori D, Street ME (2011) A systems biology approach: new insights into fetal growth restriction using Bayesian networks. J Biol Regul Homeost Agents 25(2):269–277

    PubMed  CAS  Google Scholar 

  • Garcia-Lloret MI, Yui J, Winkler-Lowen B, Guilbert LJ (1996) Epidermal growth factor inhibits cytokine-induced apoptosis of primary human trophoblasts. J Cell Physiol 167:324–332

    Article  PubMed  CAS  Google Scholar 

  • Ghidini A (1996) Idiopathic fetal growth restriction: a pathophysiologic approach. Obstet Gynecol Surv 51(6):376–382

    Article  PubMed  CAS  Google Scholar 

  • Hadlock FP, Harrist RB, Martinez P (1991) In utero analysis of fetal growth: a sonographic weight standard. Radiology 181(1):129–133

    PubMed  CAS  Google Scholar 

  • Hadlock FP, Shah YP, Kanon DJ, Lindsey JV (1992) Fetal crown-rump length: reevaluation of relation to menstrual age (5e18 weeks) with high resolution real-time US. Radiology 182:501–505

    PubMed  CAS  Google Scholar 

  • Haider S, KnÖfler M (2009) Human tumour necrosis factor: physiological and pathological roles in placenta and endometrium. Placenta 30:111–123

    Article  PubMed  CAS  Google Scholar 

  • Hill JA, Polgar K, Anderson DJ (1995) T-helper 1-type immunity to trophoblast in women with recurrent spontaneous abortion. JAMA 273(24):1933–1936

    Article  PubMed  CAS  Google Scholar 

  • Holcberg G, Huleihel M, Sapir O, Katz M, Tsadkin M, Furman B, Mazor M, Myatt L (2001) Increased production of tumor necrosis factor-alpha by IUGR human placentae. Eur J Obstet Gynecol Reprod Biol 94:69–72

    Article  PubMed  CAS  Google Scholar 

  • Hung TH, Charnock-Jones DS, Skepper JN, Burton GJ (2004) Secretion of tumor necrosis factor-alpha from human placental tissues induced by hypoxiareoxygenation causes endothelial cell activation in vitro: a potential mediator of the inflammatory response in preeclampsia. Am J Pathol 164:1049–1061

    Article  PubMed  CAS  Google Scholar 

  • Hunt JS, Atherton RA, Pace JL (1990) Differential responses of rat trophoblast cells and embryonic fibroblasts to cytokines that regulate proliferation and class 1 MHC antigen expression. J Immunol 145:184–191

    PubMed  CAS  Google Scholar 

  • Hunt JS, Chen HL, Hu XL, Tabibzadeh S (1992) Tumor necrosis factor-alpha messenger ribonucleic acid and protein in human endometrium. Biol Reprod 47:141–147

    Article  PubMed  CAS  Google Scholar 

  • Hunt JS, Chen H, Hu X, Pollard JW (1993) Normal distribution of tumor necrosis factor-a messenger ribonucleic acid and protein in the uteri, placentas, and embryos of osteopetrotic (op/op) mice lacking colony stimulating factor-1. Biol Reprod 49:441–452

    Article  PubMed  CAS  Google Scholar 

  • King A, Jokhi PP, Smith SK, Sharkey AM, Loke YW (1995) Screening for cytokine mRNA in human villous and extravillous trophoblasts using the reversetranscriptase polymerase chain reaction (RT-PCR). Cytokine 7:364–371

    Article  PubMed  CAS  Google Scholar 

  • Kupferminc MJ, Peaceman AM, Wigton TR, Rehnberg KA, Socol ML (1994) Tumor necrosis factor-alpha is elevated in plasma and amniotic fluid of patients with severe preeclampsia. Am J Obstet Gynecol 170:1752–1757

    PubMed  CAS  Google Scholar 

  • Lachapelle MH, Miron P, Hemmings R, Falcone T, Granger L, Bourque J, Langlais J (1993) Embryonic resistance to tumor necrosis factor-a mediated cytotoxicity: novel mechanism underlying maternal immunological tolerance to the fetal allograft. Hum Reprod 7:1032–1038

    Google Scholar 

  • Lyall F, Bulmer JN, Kelly H, Duffie E, Robson SC (1999) Human trophoblast invasion and spiral artery transformation: the role of nitric oxide. Am J Pathol 154:1105–1114

    Article  PubMed  CAS  Google Scholar 

  • Nawroth PP, Stern DM (1986) Modulation of endothelial cells hemostatic properties by tumor necrosis factor. J Exp Med 163:740–745

    Article  PubMed  CAS  Google Scholar 

  • Pijnenborg R, McLaughlin PJ, Vercruysse L, Hanssens M, Johnson PM, Keith JC Jr, Van Assche FA (1998) Immunolocalization of tumour necrosis factor-alpha (TNF alpha) in the placental bed of normotensive and hypertensive human pregnancies. Placenta 19(4):231–239

    Article  PubMed  CAS  Google Scholar 

  • Resnik R (2002) Intrauterine growth restriction. Obstet Gynecol 99:490–496

    Article  PubMed  Google Scholar 

  • Saito S, Umekage H, Sakamoto Y, Sakai M, Tanebe K, Sasaki Y, Morikawa H (1999) Increased T-helper-1-type immunity and decreased T-helper-2-type immunity in patients with preeclampsia. Am J Reprod Immunol 41(5):297–306

    Article  PubMed  CAS  Google Scholar 

  • Sankaran S, Kyle PM (2009) Aetiology and pathogenesis of IUGR. Best Pract Res Clin Obstet Gynecol 23:765–777

    Article  Google Scholar 

  • Seremak-Mrozikiewicz A, Dubiel M, Drews K, Gudmundsson S, Mrozikiewicz PM (2008) TNF-alpha gene polymorphism and fetal Doppler velocimetry in intrauterine growth restriction. Neuro Endocrinol Lett 29(4):493–499

    PubMed  CAS  Google Scholar 

  • Simmons DG, Fortier AL, Cross JC (2007) Diverse subtypes and developmental origins of trophoblast giant cells in the mouse placenta. Dev Biol 304:567–578

    Article  PubMed  CAS  Google Scholar 

  • Spong CY, Scherer DM, Ghidini A, Pezzullo JC, Salafia CM, Eglinton GS (1997) Midtrimester amniotic fluid tumor necrosis factor-alpha does not predict small-for gestational-age infants. Am J Reprod Immunol 37:236–239

    Article  PubMed  CAS  Google Scholar 

  • Stallmach T, Hebisch G, Joller H, Kolditz P, Engelmann M (1995) Expression pattern of cytokines in the different compartments of the feto-maternal unit under various conditions. Reprod Fertil Dev 7:1573–1580

    Article  PubMed  CAS  Google Scholar 

  • Taylor CR (1993) Appl Immunohistochem 1:232–243

    Google Scholar 

  • Tosun M, Celik H, Avci B, Yavuz E, Alper T, Malatyalioğlu E (2010) Maternal and umbilical serum levels of interleukin-6, interleukin-8, and tumor necrosis factor-alpha in normal pregnancies and in pregnancies complicated by preeclampsia. J Matern Fetal Neonatal Med 23(8):880–886

    Article  PubMed  CAS  Google Scholar 

  • Vince G, Shorter S, Starkey P, Humphreys J, Clover L, Wilkins T, Sargent I, Redman C (1992) Localization of tumour necrosis factor production in cells at the materno/fetal interface in human pregnancy. Clin Exp Immunol 88(1):174–180

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Du F, Wang X (2008) TNF-alpha induces two distinct caspase-8 activation pathways. Cell 133:693–703

    Article  PubMed  CAS  Google Scholar 

  • WHO (1995) Expert committee report: physical status: the use and interpretation of anthropometry. Technical Report Series. 854. World Health Organization, Geneva

  • Williams RL, Creasy RK, Cunningham GC, Hawes WE, Norris FD, Tashiro M (1982) Fetal growth and perinatal viability in California. Obstet Gynecol 59:624–632

    PubMed  CAS  Google Scholar 

  • Wride MA, Sanders EJ (1995) Potential roles for tumour necrosis factor-α during embryonic development. Anat Embryol 191:1–10

    Article  PubMed  CAS  Google Scholar 

  • Yang Y, Yelavarthi KK, Chen HL, Pace JL, Terranova PF, Hunt JS (1993) Molecular, biochemical, and functional characteristics of tumor necrosis factor-alpha produced by human placental cytotrophoblastic cells. J Immunol 150:5614–5624

    PubMed  CAS  Google Scholar 

  • Yelavarthi KK, Hunt JS (1993) Analysis of p60 and p80 tumor necrosis factor-a receptor messenger RNA and protein in human placentas. Am J Pathol 143:1131–1141

    PubMed  CAS  Google Scholar 

  • Yu X, Wang L, Yan C, Li X (2007) Expression and localization of tumor necrosis factor receptor 1 protein in the chorionic villi in early normal and spontaneous abortion. Eur J Obstet Gynecol Reprod Biol 132:58–63

    Article  PubMed  CAS  Google Scholar 

  • Yui J, Garcia-Lloret M, Wegmann TG, Guilbert LJ (1994) Cytotoxicity of tumor necrosis factor alpha and gamma-interferon against primary human placental trophoblasts. Placenta 15:819–835

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia for continuous help and support. Thanks to research assistances for their help in recording and filing the research data.

Conflict of interest

This work was supported by grant no. 29/230 from King Abdulaziz City for Science and Technology; Kingdom of Saudi Arabia.

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Authors and Affiliations

  1. Department of Anatomy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia

    Shaima M. Almasry & Magda A. Eldomiaty

  2. Department of Anatomy, Al-Mansoura University, Al-Mansoura, Egypt

    Shaima M. Almasry

  3. Department of Anatomy, Tanta University, Tanta, Egypt

    Magda A. Eldomiaty

  4. Department of Obstetrics and Gynecology, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia

    Amr K. Elfayomy & Fawzia A. Habib

  5. Department of Obstetrics and Gynecology, Zagazig University, Zagazig, Egypt

    Amr K. Elfayomy

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  1. Shaima M. Almasry
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Correspondence to Shaima M. Almasry.

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Almasry, S.M., Eldomiaty, M.A., Elfayomy, A.K. et al. Expression pattern of tumor necrosis factor alpha in placentae of idiopathic fetal growth restriction. J Mol Hist 43, 253–261 (2012). https://doi.org/10.1007/s10735-012-9410-6

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