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Published in: Diagnostic Pathology 1/2010

Open Access 01-12-2010 | Research

Intrauterine growth restriction and placental angiogenesis

Authors: Figen Barut, Aykut Barut, Banu Dogan Gun, Nilufer Onak Kandemir, Mehmet Ibrahim Harma, Muge Harma, Erol Aktunc, Sukru Oguz Ozdamar

Published in: Diagnostic Pathology | Issue 1/2010

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Abstract

Background

Vascular endothelial growth factor (VEGF), basic-fibroblast growth factor (b-FGF), and endothelial nitric oxide synthase (eNOS) are factors that take part in placental angiogenesis. They are highly expressed during embryonic and fetal development, especially in the first trimester. In this study, we aimed to investigate the role of placental angiogenesis in the development of intrauterine growth restriction (IUGR) by comparing the levels of expression of VEGF-A, b-FGF, and eNOS in normal-term pregnancy and IUGR placentas.

Methods

The expression of VEGF-A, b-FGF, and eNOS was studied using the avidin-biotin-peroxidase method in placental tissues diagnosed as normal (n = 55) and IUGR (n = 55). Results were evaluated in a semi-quantitative manner.

Results

The expression of all the markers was significantly higher (p < 0.001) in cytotrophoblasts, syncytiotrophoblasts, extravillous trophoblasts, vascular smooth muscle cells, chorionic villous stromal cells, and villous vascular endothelial cells of the IUGR placentas when compared with those collected from normal-term pregnancies.

Conclusion

Increased expression of VEGF-A, b-FGF, and eNOS may be the result of inadequate uteroplacental perfusion, supporting the proposal that abnormal angiogenesis plays a role in the pathophysiology of IUGR.
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Literature
1.
go back to reference Gurel D, Özer E, Altunyurt S, Guclu S, Demir N: Expression of IGR-IR and VEGF and trophoblastic proliferative activity in placentas from pregnancies complicated by IUGR. Pathol Res Pract. 2003, 199: 803-809. 10.1078/0344-0338-00499.CrossRefPubMed Gurel D, Özer E, Altunyurt S, Guclu S, Demir N: Expression of IGR-IR and VEGF and trophoblastic proliferative activity in placentas from pregnancies complicated by IUGR. Pathol Res Pract. 2003, 199: 803-809. 10.1078/0344-0338-00499.CrossRefPubMed
2.
go back to reference Maulik D, Evans JF, Ragolia L: Fetal growth restriction: Pathogenic mechanisms. Clin Obstet Gynecol. 2006, 49: 219-227. 10.1097/00003081-200606000-00005.CrossRefPubMed Maulik D, Evans JF, Ragolia L: Fetal growth restriction: Pathogenic mechanisms. Clin Obstet Gynecol. 2006, 49: 219-227. 10.1097/00003081-200606000-00005.CrossRefPubMed
3.
go back to reference Arroyo JA, Winn VD: Vasculogenesis and angiogenesis in the IUGR placenta. Semin Perinatol. 2008, 32: 172-177. 10.1053/j.semperi.2008.02.006.CrossRefPubMed Arroyo JA, Winn VD: Vasculogenesis and angiogenesis in the IUGR placenta. Semin Perinatol. 2008, 32: 172-177. 10.1053/j.semperi.2008.02.006.CrossRefPubMed
4.
go back to reference Ahmed A, Perkins J: Angiogenesis and intrauterine growth restriction. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000, 14: 981-998. 10.1053/beog.2000.0139.CrossRefPubMed Ahmed A, Perkins J: Angiogenesis and intrauterine growth restriction. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000, 14: 981-998. 10.1053/beog.2000.0139.CrossRefPubMed
5.
go back to reference Özkan S, Vural B, Dalçık C, Taş A, Dalçık H: Placental expression of insulin-like growth factor-I, fibroblast growth factor-basic and neural cell adhesion molecule in pregnancies with small for gestational age fetuses. J Perinatol. 2008, 28: 468-474. 10.1038/jp.2008.27.CrossRefPubMed Özkan S, Vural B, Dalçık C, Taş A, Dalçık H: Placental expression of insulin-like growth factor-I, fibroblast growth factor-basic and neural cell adhesion molecule in pregnancies with small for gestational age fetuses. J Perinatol. 2008, 28: 468-474. 10.1038/jp.2008.27.CrossRefPubMed
6.
go back to reference Shiraishi S, Nakagawa K, Kinukawa N, Nakano H, Sueishi K: Immunuhistochemical localization of vascular endothelial growth factor in the human placenta. Placenta. 1996, 17: 111-121. 10.1016/S0143-4004(96)80004-X.CrossRefPubMed Shiraishi S, Nakagawa K, Kinukawa N, Nakano H, Sueishi K: Immunuhistochemical localization of vascular endothelial growth factor in the human placenta. Placenta. 1996, 17: 111-121. 10.1016/S0143-4004(96)80004-X.CrossRefPubMed
7.
go back to reference Pardi G, Marconi AM, Cetin I: Pathophysiology of intrauterine growth retardation: role of the placenta. Acta Paediatr. 1997, 423 (Suppl): 170-172.CrossRef Pardi G, Marconi AM, Cetin I: Pathophysiology of intrauterine growth retardation: role of the placenta. Acta Paediatr. 1997, 423 (Suppl): 170-172.CrossRef
8.
go back to reference Frater JL, Kay NE, Goolsby CL, Crawford SE, Dewald GW, Peterson LC: Dysregulated angiogenesis in B-chronic lymphocytic leukemia: Morphologic, immunohistochemical, and flow cytometric evidence. Diagn Pathol. 2008, 3: 16-10.1186/1746-1596-3-16.PubMedCentralCrossRefPubMed Frater JL, Kay NE, Goolsby CL, Crawford SE, Dewald GW, Peterson LC: Dysregulated angiogenesis in B-chronic lymphocytic leukemia: Morphologic, immunohistochemical, and flow cytometric evidence. Diagn Pathol. 2008, 3: 16-10.1186/1746-1596-3-16.PubMedCentralCrossRefPubMed
9.
go back to reference Kaufmann P, Mayhew TM, Charnock-Jones DS: Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes during normal pregnancy. Placenta. 2004, 25: 114-126. 10.1016/j.placenta.2003.10.009.CrossRefPubMed Kaufmann P, Mayhew TM, Charnock-Jones DS: Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes during normal pregnancy. Placenta. 2004, 25: 114-126. 10.1016/j.placenta.2003.10.009.CrossRefPubMed
10.
go back to reference Lee MY, Huang JP, Chen YY, Aplin JD, Wu YH, Chen CY, Chen PC, Chen CP: Angiogenesis in differentiated placental multipotent mesenchymal stromal cells is dependent on integrin alpha5beta1. PLoS One. 2009, 4: e6913-10.1371/journal.pone.0006913.PubMedCentralCrossRefPubMed Lee MY, Huang JP, Chen YY, Aplin JD, Wu YH, Chen CY, Chen PC, Chen CP: Angiogenesis in differentiated placental multipotent mesenchymal stromal cells is dependent on integrin alpha5beta1. PLoS One. 2009, 4: e6913-10.1371/journal.pone.0006913.PubMedCentralCrossRefPubMed
11.
go back to reference Nakagawa Y, Fujimoto J, Tamaya T: Placental growth by the estrogen-dependent angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor, throughout gestation. Gynecol Endocrinol. 2004, 19: 259-266. 10.1080/09513590400016201.CrossRefPubMed Nakagawa Y, Fujimoto J, Tamaya T: Placental growth by the estrogen-dependent angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor, throughout gestation. Gynecol Endocrinol. 2004, 19: 259-266. 10.1080/09513590400016201.CrossRefPubMed
12.
go back to reference Helske S, Vuorela P, Carpén O, Hornig C, Weich H, Halmesmäki E: Expression of vascular endothelial growth factor receptors 1, 2 and 3 in placentas from normal and complicated pregnancies. Mol Hum Reprod. 2001, 7: 205-210. 10.1093/molehr/7.2.205.CrossRefPubMed Helske S, Vuorela P, Carpén O, Hornig C, Weich H, Halmesmäki E: Expression of vascular endothelial growth factor receptors 1, 2 and 3 in placentas from normal and complicated pregnancies. Mol Hum Reprod. 2001, 7: 205-210. 10.1093/molehr/7.2.205.CrossRefPubMed
13.
go back to reference Hamai Y, Fujli T, Yamashita T, Kozuma S, Okai T, Taketani Y: Evidence for basic fibroblast growth factor as a crucial angiogenic growth factor, released from human trophoblasts during early gestation. Placenta. 1998, 19: 149-155. 10.1016/S0143-4004(98)90003-0.CrossRefPubMed Hamai Y, Fujli T, Yamashita T, Kozuma S, Okai T, Taketani Y: Evidence for basic fibroblast growth factor as a crucial angiogenic growth factor, released from human trophoblasts during early gestation. Placenta. 1998, 19: 149-155. 10.1016/S0143-4004(98)90003-0.CrossRefPubMed
14.
go back to reference Myatt L, Eis ALW, Brockman DE, Greer IA, Lyall F: Endothelial nitric oxide synthase in placental villous tissue from normal, pre-eclamptic and intrauterine growth restricted pregnancies. Hum Reprod. 1997, 12: 167-172. 10.1093/humrep/12.1.167.CrossRefPubMed Myatt L, Eis ALW, Brockman DE, Greer IA, Lyall F: Endothelial nitric oxide synthase in placental villous tissue from normal, pre-eclamptic and intrauterine growth restricted pregnancies. Hum Reprod. 1997, 12: 167-172. 10.1093/humrep/12.1.167.CrossRefPubMed
15.
go back to reference Ng YS, Krilleke D, Shima DT: VEGF function in vascular pathogenesis. Exp Cell Res. 2006, 312: 527-537. 10.1016/j.yexcr.2005.11.008.CrossRefPubMed Ng YS, Krilleke D, Shima DT: VEGF function in vascular pathogenesis. Exp Cell Res. 2006, 312: 527-537. 10.1016/j.yexcr.2005.11.008.CrossRefPubMed
16.
go back to reference Galan HL, Pandipati S, Filly RA: Ultrasound evaluation of fetal biometry and normal and abnormal fetal growth. Ultrasonography in obstetrics and gynecology. Edited by: Callen PW. 2008, USA: Saunders Elsevier, 225-265. 5CrossRef Galan HL, Pandipati S, Filly RA: Ultrasound evaluation of fetal biometry and normal and abnormal fetal growth. Ultrasonography in obstetrics and gynecology. Edited by: Callen PW. 2008, USA: Saunders Elsevier, 225-265. 5CrossRef
17.
go back to reference Kinzler WL, Vintzileos AM: Fetal growth restriction. Curr Opin Obstet Gynecol. 2008, 2: 125-131.CrossRef Kinzler WL, Vintzileos AM: Fetal growth restriction. Curr Opin Obstet Gynecol. 2008, 2: 125-131.CrossRef
18.
go back to reference Mayhew TM, Charnock-Jones DS, Kaufmann P: Aspects of human fetoplacental vasculogenesis and angiogenesis. III. Changes in complicated pregnancies. Placenta. 2004, 25: 127-139. 10.1016/j.placenta.2003.10.010.CrossRefPubMed Mayhew TM, Charnock-Jones DS, Kaufmann P: Aspects of human fetoplacental vasculogenesis and angiogenesis. III. Changes in complicated pregnancies. Placenta. 2004, 25: 127-139. 10.1016/j.placenta.2003.10.010.CrossRefPubMed
19.
go back to reference Benirschke K: Recent trends in chorangiomas, especially those of multiple and recurrent chorangiomas. Pediatr Dev Pathol. 1999, 2: 264-269. 10.1007/s100249900122.CrossRefPubMed Benirschke K: Recent trends in chorangiomas, especially those of multiple and recurrent chorangiomas. Pediatr Dev Pathol. 1999, 2: 264-269. 10.1007/s100249900122.CrossRefPubMed
20.
go back to reference Lyall F, Young A, Boswell F, Kingdom JCP, Greer IA: Placental expression of vascular endothelial growth factor in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth restriction does not support placental hypoxia at delivery. Placenta. 1997, 18: 269-276. 10.1016/S0143-4004(97)80061-6.CrossRefPubMed Lyall F, Young A, Boswell F, Kingdom JCP, Greer IA: Placental expression of vascular endothelial growth factor in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth restriction does not support placental hypoxia at delivery. Placenta. 1997, 18: 269-276. 10.1016/S0143-4004(97)80061-6.CrossRefPubMed
Metadata
Title
Intrauterine growth restriction and placental angiogenesis
Authors
Figen Barut
Aykut Barut
Banu Dogan Gun
Nilufer Onak Kandemir
Mehmet Ibrahim Harma
Muge Harma
Erol Aktunc
Sukru Oguz Ozdamar
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2010
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-5-24

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