Home Medicine Recombinant vascular endothelial growth factor 121 injection for the prevention of fetal growth restriction in a preeclampsia mouse model
Article
Licensed
Unlicensed Requires Authentication

Recombinant vascular endothelial growth factor 121 injection for the prevention of fetal growth restriction in a preeclampsia mouse model

  • Sri Sulistyowati , Muhammad Adrianes Bachnas EMAIL logo , Nuri Dyah Anggraini , Eric Edwin Yuliantara , Wisnu Prabowo , Nutria Widya Purna Anggraini , Mochammad Besari Adi Pramono , Adityawarman , Erry Gumilar Dachlan and Wiku Andonotopo
Published/Copyright: December 10, 2016

Abstract

Aim:

To discover the potential role of recombinant VEGF121 (rVEGF121) injection for the prevention of fetal growth restriction in a preeclampsia (PE) mouse model (Mus musculus).

Subjects and methods:

This is an experimental study of 30 pregnant mice that were randomly divided into three groups: normal, PE, and PE with rVEGF121 injection. The PE mouse model was created by injecting anti Qa-2 10 ng iv, which is deleterious to Qa-2 expression (homologous to HLA-G), from the first to the fourth day of gestation. PE was validated by measuring serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor(PIGF) and also by kidney histopathology. Recombinant VEGF121 was given on the ninth day until the 11th day of pregnancy; mice were terminated on the 16th day. Fetal weights were acquired with a Denver analytical balance. Serum levels of sFlt-1 and PlGF were measured using enzyme-linked immunosorbent assay (ELISA). The data were statistically analyzed via analysis of variance (ANOVA).

Results:

On average, fetal birth weight was 0.7150 g in the normal group, 0.4936 g in the PE group, and 0.6768 g in the PE with rVEGF121 injection group. ANOVA showed significant growth restriction in the PE group (P=0.006), confirming the use of anti Qa-2 as a suitable PE model. Kidney histopathology results, sFlt-1 levels, and PlGF levels also demonstrated that anti Qa-2 consistently conferred hallmarks of PE in mice. Vascular endothelial growth factor (VEGF) injection prevented fetal growth restriction; comparable fetal weights were observed between the PE model with VEGF treatment and the normal group (P=0.610) but differed from the untreated PE group (P=0.021).

Conclusions:

Injection of rVEGF121 has the potential to prevent fetal growth restriction in a newly proposed PE mouse model.


Corresponding author: Muhammad Adrianes Bachnas, MD, Maternal-Fetal Medicine Sub-Division, Department of Obstetrics and Gynecology, Faculty of Medicine Sebelas Maret University, Dr. Moewardi General Hospital, Jl.Kol Sutarto, 132, Solo-Indonesia, Tel.: +628122692928

References

[1] Ananth CV, Keyes KM, Wapner RJ. Preeclampsia rates in the United States, 1980–2010: age-period-cohort analysis. Br Med J. 2013;347:1–9.10.1097/01.aoa.0000455580.95071.e1Search in Google Scholar

[2] Srinivas SK, Edlow AG, Neff PM, Sammel MD, Andrela CM, Elovitz MA. Rethinking IUGR in preeclampsia: dependent or independent of maternal hypertension? J Perinatol. 2009;29:680–4.10.1038/jp.2009.83Search in Google Scholar PubMed PubMed Central

[3] Creasy RK, Resnik R. Maternal-fetal medicine. Principle and practice. 7th edition. Philadelphia: Elsevier; 2013.Search in Google Scholar

[4] Hagmann H, Thadhani R, Benzing T, Karumanchi SA, Stepan H. The promise of angiogenic markers for the early diagnosis and prediction of preeclampsia. Clin Chem. 2012;58:837–45.10.1373/clinchem.2011.169094Search in Google Scholar PubMed

[5] Bdolah Y, Sukhatme VP, Karumanchi SA. Angiogenic imbalance in the patophysiology of preeclampsia: newer insight. Semin Nephrol. 2004;24:548–56.10.1016/j.semnephrol.2004.07.003Search in Google Scholar

[6] Comiskey M, Warner CM, Schust DJ. MHC molecules of preimplantation embryo and trophoblast. Immunology of Pregnancy. 2006;13:130–47.10.1007/0-387-34944-8_13Search in Google Scholar

[7] Lyall F,Robson SC,Bulmer JN. Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction. Hypertension. 2013;62:1046–54.10.1161/HYPERTENSIONAHA.113.01892Search in Google Scholar PubMed

[8] Mateus J, Bytautiene E, Lu F, Tamayo EH, Betancourt A, Hankins GD, et al. Endothelial growth factor therapy improves preeclampsia like manifestation in murine model induced by expression of SVEGFR-1. Am J Physiol Heart Circ Physiol. 2011;301:1781–7.10.1152/ajpheart.00373.2011Search in Google Scholar PubMed

[9] Li Z, Zhang Y, Ying Ma J, Kapoun AM, Shao Q, Kerr I, et al. Recombinant vascular endothelial growth factor 121 attenuates hypertension and improves kidney damage in a rat model of preeclampsia. Hypertension. 2007;50:686–92.10.1161/HYPERTENSIONAHA.107.092098Search in Google Scholar PubMed

[10] Gilbert JS, Verzwyvelt J, Colson D, Arany M, Karumanchi SA, Granger JP. Recombinant vascular endothelial growth factor 121 infusion lowers blood pressure and improves renal function in rats with placental ischemia-induced hypertension. Hypertension. 2010;55:380–5.10.1161/HYPERTENSIONAHA.109.141937Search in Google Scholar PubMed PubMed Central

[11] David AL, Torondel B, Zachary I, Wigley V, Nader KA, Mehta V, et al. Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep. Gene Therapy. 2008;15:1344–50.10.1038/gt.2008.102Search in Google Scholar PubMed

[12] Woods AK, Hoffmann DS, Weydert CJ, Butler SD, Zhou Y, Sharma RV, Davisson RL. Adenoviral delivery of VEGF 121 early in pregnancy prevents spontaneous development of preeclampsia in BPH/5 Mice. Hypertension. 2011;57:94–102.10.1161/HYPERTENSIONAHA.110.160242Search in Google Scholar

[13] Sulistyowati S, Abadi A, Hood J, Soetjipto S. The influence of low HLA-G protein expression on HSP-70 and VCAM-1 profile in preeclampsia. Indonesian J Obstet Gynecol. 2010;34:185–90.10.1016/S0020-7292(12)61090-XSearch in Google Scholar

[14] Sulistyowati S, Abadi A, Wijiati W. Low class Ib (HLA-G/Qa-2) MHC protein expression against Hsp-70 and VCAM-1 profile on preeclampsia. An observation on experimental animal Mus Musculus with endothelial dysfunction model. Indonesian J Obstet Gynecol. 2010;34:103–7.Search in Google Scholar

[15] Gilbert JS, Babcock SA, Granger JP. Hypertension produced by reduced uterine perfusion in pregnant rats is associated with increased soluble fms like tyrosine kinase-1 expression. Hypertension. 2007;50:1142–7.10.1161/HYPERTENSIONAHA.107.096594Search in Google Scholar PubMed

[16] Smith GC, Crossley JA, Aitken DA, Jenkins N, Lyall F, Cameron AD, et al. Circulating angiogenic factors in early pregnancy and the risk of preeclampsia, intrauterine growth restriction, spontaneous preterm birth, and stillbirth. Obstet Gynecol. 2007;109:1316–24.10.1097/01.AOG.0000265804.09161.0dSearch in Google Scholar PubMed

  1. The authors stated that there are no conflicts of interest regarding the publication of this article.

Received: 2016-2-1
Accepted: 2016-10-27
Published Online: 2016-12-10
Published in Print: 2017-2-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Fetal diagnosis and therapy: a continously evolving discipline
  4. Highlight articles
  5. Prenatally diagnosed fetal tumors of the head and neck: a systematic review with antenatal and postnatal outcomes over the past 20 years
  6. Prenatal screening for microcephaly: an update after three decades
  7. Fetal echocardiography: reference values for the Chinese population
  8. Multi-fetal pregnancy reduction (MFPR) to twins or singleton – medical justification and ethical slippery slope
  9. Combined screening test for trisomy 21 – is it as efficient as we believe?
  10. Fetal loss following invasive prenatal testing: a comparison of transabdominal chorionic villus sampling, transcervical chorionic villus sampling and amniocentesis
  11. Comparison of adverse perinatal outcomes after single-needle and double-needle CVS techniques
  12. Prenatal decision-making in the second and third trimester in trisomy 21-affected pregnancies
  13. Role of collagen type IV in the pathogenesis of increased prenasal thickness in Down syndrome fetuses: sonographic and immunohistological findings
  14. Congenital diaphragmatic hernia: endotracheal fluid phospholipidic profile following tracheal occlusion in an experimental model
  15. Original articles
  16. The effect of intraumbilical fetal nutrition via a subcutaneously implanted port system on amino acid concentration by severe IUGR human fetuses
  17. Anti-inflammatory Elafin in human fetal membranes
  18. Recombinant vascular endothelial growth factor 121 injection for the prevention of fetal growth restriction in a preeclampsia mouse model
  19. Estimation of fetal weight by ultrasonography after preterm premature rupture of membranes: comparison of different formulas
  20. Congress Calendar
  21. Congress Calendar
Downloaded on 31.12.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jpm-2016-0149/html
Scroll to top button