Skip to main content
Log in

Vascular endothelial growth factor in monochorionic twins with twin-twin transfusion syndrome

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Objective: The purpose of this study was to determine vascular endothelial growth factor (VEGF) concentrations in the donor and the recipient in monochorionic twin pregnancies with twin-twin transfusion syndrome (TTTS) and single pregnancies in order to investigate the involvement of VEGF in the pathophysiology of TTTS. Methods: Six twin pregnancies in 11 monochorionic twin pregnancies complicated with TTTS and 11 single control pregnancies were compared. Gestational age-matched fetal blood and placental samples were obtained at birth. Serum VEGF concentration in the umbilical vein was measured by an enzymelinked immunoabsorbant assay. Tissue protein expression of VEGF was determined by using immunohistochemistry. Western blot analysis and scanning densitometry were used to quantify and compare the VEGF expression in the terminal villi. Results: Serum VEGF concentrations in the umbilical vein in both donors and recipients tended to be higher than those in the controls. Immunolocalization of VEGF in terminal villous placenta samples in both donors and recipients was mainly observed in the syncytiotrophoblastic layer and vascular endothelial cells with less intense staining in stromal cells. The expression of VEGF in the donor placenta increased significantly (p=0.006) compared to that in the control placenta, but the expression of VEGF in the recipients tended to be higher than in the controls. Conclusion: Intrauterine circulatory imbalance may induce changes in VEGF expression and these alterations may be involved in both donor and recipient in the pathogenesis of TTTS, due to the maintenance of hemodynamic stability between the circulation of the twins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Steinberg LH, Hurley VA, Desmedt E, Beischer NA. Acute polyhydramnios in twin pregnancies. Aust N Z J Obstet Gynaecol 1990, 30: 196–200.

    Article  PubMed  CAS  Google Scholar 

  2. Bajoria R, Wigglesworth J, Fisk NM. Angioarchitecture of monochorionic placentas in relation to the twin-twin transfusion syndrome. Am J Obstet Gynecol 1995, 172: 856–63.

    Article  PubMed  CAS  Google Scholar 

  3. Bajoria R. Vascular anatomy of monochorionic placenta in relation to discordant growth and amniotic fluid volume. Hum Reprod 1998, 13: 2933–40.

    Article  PubMed  CAS  Google Scholar 

  4. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989, 246: 1306–9.

    Article  PubMed  CAS  Google Scholar 

  5. Poole TJ, Coffin JD. Vasculogenesis and angiogenesis: two distinct morphogenetic mechanisms establish embryonic vascular pattern. J Exp Zool 1989, 251: 224–31.

    Article  PubMed  CAS  Google Scholar 

  6. Ferrara N, Houck K, Jakeman L, Leung DW. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 1992, 13: 18–32.

    Article  PubMed  CAS  Google Scholar 

  7. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983, 219: 983–5.

    Article  PubMed  CAS  Google Scholar 

  8. Jackson MR, Carney EW, Lye SJ, Ritchie JW. Localization of two angiogenic growth factors (PDECGF and VEGF) in human placentae throughout gestation. Placenta 1994, 15: 341–53.

    Article  PubMed  CAS  Google Scholar 

  9. Clark DE, Smith SK, Sharkey AM, Charnock-Jones DS. Localization of VEGF and expression of its receptors flt and KDR in human placenta throughout pregnancy. Hum Reprod 1996, 11: 1090–8.

    Article  PubMed  CAS  Google Scholar 

  10. Sharkey AM, Charnock-Jones DS, Boocock CA, Brown KD, Smith SK. Expression of mRNA for vascular endothelial growth factor in human placenta. J Reprod Fertil 1993, 99: 609–15.

    Article  PubMed  CAS  Google Scholar 

  11. Anthony FW, Wheeler T, Elcock CL, Pickett M, Thomas EJ. Short report: identification of a specific pattern of vascular endothelial growth factor mRNA expression in human placenta and cultured placental fibroblasts. Placenta 1994, 15: 557–61.

    Article  PubMed  CAS  Google Scholar 

  12. Shiraishi S, Nakagawa K, Kinukawa N, Nakano H, Sueishi K. Immunohistochemical localization of vascular endothelial growth factor in the human placenta. Placenta 1996, 17: 111–21.

    Article  PubMed  CAS  Google Scholar 

  13. Bates DO, Lodwick D, Williams B. Vascular endothelial growth factor and microvascular permeability. Microcirculation 1999, 6: 83–96.

    Article  PubMed  CAS  Google Scholar 

  14. Svedas E, Islam KB, Nisell H, Kublickiene KR. Vascular endothelial growth factor induced functional and morphologic signs of endothelial dysfunction in isolated arteries from normal pregnant women. Am J Obstet Gynecol 2003, 188: 168–76.

    Article  PubMed  CAS  Google Scholar 

  15. Kroll J, Waltenberger J. VEGF-A induces expression of eNOS and iNOS in endothelial cells via VEGF receptor-2 (KDR). Biochem Biophys Res Commun 1998, 252: 743–6.

    Article  PubMed  CAS  Google Scholar 

  16. Bauters C, Asahara T, Zheng LP, et al. Recovery of disturbed endothelium-dependent flow in the collateral-perfused rabbit ischemic hindlimb after administration of vascular endothelial growth factor. Circulation 1995, 91: 2802–9.

    Article  PubMed  CAS  Google Scholar 

  17. Quintero RA, Morales WJ, Allen MH, Bornick PW, Johnson PK, Kruger M. Staging of twin-twin transfusion syndrome. J Peinatol 1999, 19: 550–5.

    Article  CAS  Google Scholar 

  18. Krukier II, Pogorelova TN. Production of vascular endothelial growth factor and endothelin in the placenta and umbilical cord during normal and complicated pregnancy. Bull Exp Biol Med 2006, 141: 216–8.

    Article  PubMed  CAS  Google Scholar 

  19. Brown MD, Hudlicka O. Modulation of physiological angiogenesis in skeletal muscle by mechanical forces: involvement of VEGF and metalloproteinases. Angiogenesis 2003, 6: 1–14.

    Article  PubMed  CAS  Google Scholar 

  20. Karimu AL, Burton GJ. Significance of changes in fetal perfusion pressure to factors controlling angiogenesis in the human term placenta. J Reprod Fertil 1994, 102: 447–50.

    Article  PubMed  CAS  Google Scholar 

  21. Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992, 359: 843–5.

    Article  PubMed  CAS  Google Scholar 

  22. Kumazaki K, Nakayama M, Suehara N, Wada Y. Expression of vascular endothelial growth factor, placental growth factor, and their receptors Flt-1 and KDR in human placenta under pathologic conditions. Hum Pathol 2002, 33: 1069–77.

    Article  PubMed  CAS  Google Scholar 

  23. Mahieu-Caputo D, Salomon LJ, Le Bidois J, et al. Fetal hypertension: an insight into the pathogenesis of the twin-twin transfusion syndrome. Prenat Diagn 2003, 23: 640–5.

    Article  PubMed  CAS  Google Scholar 

  24. Tolosa J, Zoppini C, Ludomirsky A, et al. Fetal hypertension and cardiac hypertrophy in the discordant twin syndrome. Am J Obstet Gynecol 1993, 168: 292 (abstract).

    Google Scholar 

  25. Bajoria R, Sullivan M, Fisk NM. Endothelin concentration in monochorionic twins with severe twin-twin transfusion syndrome. Hum Reprod 1999, 14: 1614–8.

    Article  PubMed  CAS  Google Scholar 

  26. Bajoria R, Ward S, Chatterjee R. Natriuretic peptides in pathogenesis of cardiac dysfunction in the recipient fetus of twin-twin transfusion syndrome. Am J Obstet Gynecol 2002, 186: 121–7.

    Article  PubMed  CAS  Google Scholar 

  27. Bagnato A, Spinella F. Emerging role of endothelin-1 in tumor angiogenesis. Trends Endocrinol Metab 2003, 14: 44–50.

    Article  PubMed  CAS  Google Scholar 

  28. Sane DC, Anton L, Brosnihan KB. Angiogenic growth factors and hypertension. Angiogenesis 2004, 7: 193–201.

    Article  PubMed  CAS  Google Scholar 

  29. Okuda Y, Tsurumaru K, Suzuki S, et al. Hypoxia and endothelin-1 induce VEGF production in human vascular smooth muscle cells. Life Sci 1998,63: 477–84.

    Article  PubMed  CAS  Google Scholar 

  30. Lassus P, Turanlahti M, Heikkila P, et al. Pulmonary vascular endothelial growth factor and Flt-1 in fetuses, in acute and chronic lung disease, and in persistent pulmonary hypertension of the newborn. Am J Respir Crit Care Med 2001, 164: 1981–7.

    Article  PubMed  CAS  Google Scholar 

  31. Gratacós E, Van Schoubroeck D, Carreras E, et al. Transient hydrops signs in the donor fetus after laser coagulation in severe twin-twin transfusion syndrome: incidence and clinical relevance. Ultrasound Obstet Gynecol 2002, 19: 449–53.

    Article  PubMed  Google Scholar 

  32. Gratacós E, Van Schoubroeck D, Carreras E, et al. Impact of laser coagulation in severe twin-twin transfusion syndrome on fetal Doppler indices and venous blood flow volume. Ultrasound Obstet Gynecol 2002,20: 125–30.

    Article  PubMed  Google Scholar 

  33. Morine M, Maeda K, Higashino K, et al. Transient hydrops fetalis of the donor fetus in twin-twin transfusion syndrome after therapeutic amnioreduction. Ultrasound Obstet Gynecol 2003, 22: 182–5.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T. Yasui MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morine, M., Nobunaga, T., Mizutani, T. et al. Vascular endothelial growth factor in monochorionic twins with twin-twin transfusion syndrome. J Endocrinol Invest 31, 966–970 (2008). https://doi.org/10.1007/BF03345633

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345633

Key Words

Navigation