Histopathological study with immunohistochemical expression of vascular endothelial growth factor in placentas of hyperglycemic and diabetic women

Debashish Bhattacharjee; Santosh Kumar Mondal; Pratima Garain; Palash Mandal; Rudra Narayan Ray; Goutam Dey

doi:10.4103/JLP.JLP_148_16

Journal of Laboratory Physicians, Table of Contents

CC BY-NC-ND 4.0 · J Lab Physicians 2017; 9(04): 227-233
DOI: 10.4103/JLP.JLP_148_16

Original Article

Histopathological study with immunohistochemical expression of vascular endothelial growth factor in placentas of hyperglycemic and diabetic women

Debashish Bhattacharjee

Department of Pathology, Bankura Sammilani Medical College, Bankura, West Bengal, India

,

Santosh Kumar Mondal

Department of Pathology, Bankura Sammilani Medical College, Bankura, West Bengal, India

,

Pratima Garain

Department of Gynaecology and Obstetrics, Bankura Sammilani Medical College, Bankura, West Bengal, India

,

Palash Mandal

Department of Pathology, School of Medicine, Sagore Dutta Hospital, Kolkata, West Bengal, India

,

Rudra Narayan Ray

Department of Pathology, Bankura Sammilani Medical College, Bankura, West Bengal, India

,

Goutam Dey

Department of Pathology, Bankura Sammilani Medical College, Bankura, West Bengal, India

› Author Affiliations

Abstract

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Abstract

AIMS AND OBJECTIVES: Spectrum of hyperglycemia in pregnancy includes gestational diabetes mellitus (GDM), mild hyperglycemia, and overt diabetes. Many authors have worked on morphological changes of the placenta in diabetes, but few studies have correlated histopathological changes with vascular endothelial growth factor (VEGF) immunoexpression. The aim of this study was to detect different histopathological changes in various groups of diabetic placentas and to correlate with VEGF immunoexpression.

MATERIALS AND METHODS: Pregnant women were screened for diabetes. They were subsequently divided into normoglycemic (12 cases), GDM (33 cases), mild hyperglycemic (13 cases), and overt diabetes (18 cases). Placentas collected were subjected to histopathological examination. VEGF expressions were studied by immunohistochemistry.

RESULTS: Overt diabetic placenta displayed villous immaturity (44.4%), villous edema (38.9%), chorangiosis (61.1%), fibrinoid substance deposition (38.9%), and Hofbauer cell hyperplasia in 44.4% cases. GDM placentas displayed villous immaturity (45.5%), villous edema (45.5%), chorangiosis (42.4%), and fibrinoid substance deposition in 75.6% cases. Mild hyperglycemic placentas displayed villous immaturity (38.5%), chorangiosis (61.5%), and fibrinoid substance deposition in 61.5% cases. VEGF immunoexpression in GDM placentas was absent in all placental components except syncytiotrophoblast. VEGF expression in overt diabetic placentas was increased in syncytiotrophoblast and capillary endothelium compared to normoglycemic placentas. Mild hyperglycemic placentas expressed similar VEGF expression in all components when compared to normoglycemic controls. However, it displayed weak expression in vessel endothelium.

CONCLUSION: Histopathological changes in diabetic placentas might be a consequence of altered or abnormal VEGF expression in diabetic placentas. Pathogenesis and VEGF expression in GDM placentas are significantly different from overt diabetic placentas.

Key words

Gestational diabetic placentas - histopathology - vascular endothelial growth factor immunoexpression

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References

References
1 Kaufmann P, Mayhew TM, Charnock-Jones DS. Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes during normal pregnancy. Placenta 2004;25:114-26.
2 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;7:205-10.
3 Demir R, Kayisli UA, Cayli S, Huppertz B. Sequential steps during vasculogenesis and angiogenesis in the very early human placenta. Placenta 2006;27:535-9.
4 Demir R, Kayisli UA, Seval Y, Celik-Ozenci C, Korgun ET, Demir-Weusten AY, et al. Sequential expression of VEGF and its receptors in human placental villi during very early pregnancy: Differences between placental vasculogenesis and angiogenesis. Placenta 2004;25:560-72.
5 Mayhew TM. Fetoplacental angiogenesis during gestation is biphasic, longitudinal and occurs by proliferation and remodelling of vascular endothelial cells. Placenta 2002;23:742-50.
6 Kingdom J, Huppertz B, Seaward G, Kaufmann P. Development of the placental villous tree and its consequences for fetal growth. Eur J Obstet Gynecol Reprod Biol 2000;92:35-43.
7 Vaisman N, Gospodarowicz D, Neufeld G. Characterization of the receptors for vascular endothelial growth factor. J Biol Chem 1990;265:19461-6.
8 He H, Venema VJ, Gu X, Venema RC, Marrero MB, Caldwell RB. Vascular endothelial growth factor signals endothelial cell production of nitric oxide and prostacyclin through flk-1/KDR activation of c-Src. J Biol Chem 1999;274:25130-5.
9 Koch AE, Harlow LA, Haines GK, Amento EP, Unemori EN, Wong WL, et al. Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis. J Immunol 1994;152:4149-56.
10 Jakeman LB, Winer J, Bennett GL, Altar CA, Ferrara N. Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. J Clin Invest 1992;89:244-53.
11 Zhou Y, Bellingard V, Feng KT, McMaster M, Fisher SJ. Human cytotrophoblasts promote endothelial survival and vascular remodeling through secretion of Ang2, PlGF, and VEGF-C. Dev Biol 2003;263:114-25.
12 Taylor CM, Stevens H, Anthony FW, Wheeler T. Influence of hypoxia on vascular endothelial growth factor and chorionic gonadotrophin production in the trophoblast-derived cell lines: JEG, JAr and BeWo. Placenta 1997;18:451-8.
13 Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 1999;13:9-22.
14 Calderon IM, Damasceno DC, Amorin RL, Costa RA, Brasil MA, Rudge MV. Morphometric study of placental villi and vessels in women with mild hyperglycemia or gestational or overt diabetes. Diabetes Res Clin Pract 2007;78:65-71.
15 Eriksson UJ, Borg LA, Forsberg H, Styrud J. Diabetic embryopathy. Studies with animal and in vitrol models. Diabetes 1991;40 Suppl 2:94-8.
16 Zhao B, Cai J, Boulton M. Expression of placenta growth factor is regulated by both VEGF and hyperglycaemia via VEGFR-2. Microvasc Res 2004;68:239-46.
17 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.
18 Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982;144:768-73.
19 Rudge MV, Peraçoli JC, Berezowski AT, Calderon IM, Brasil MA. The oral glucose tolerance test is a poor predictor of hyperglycemia during pregnancy. Braz J Med Biol Res 1990;23:1079-89.
20 American Diabetes Association. Gestational diabetes mellitus. Diabetes Care 2004;27 Suppl 1:S88-90.
21 Gillmer MD, Beard RW, Brooke FM, Oakley NW. Carbohydrate metabolism in pregnancy. Part I. Diurnal plasma glucose profile in normal and diabetic women. Br Med J 1975;3:399-402.
22 Knox WF, Fox H. Villitis of unknown aetiology: Its incidence and significance in placentae from a British population. Placenta 1984;5:395-402.
23 Gheorman L, Plesea IE, Gheorman V. Histopathological considerations of placenta in pregnancy with diabetes. Rom J Morphol Embryol 2012;53:329-36.
24 Altshuler G. Chorangiosis. An important placental sign of neonatal morbidity and mortality. Arch Pathol Lab Med 1984;108:71-4.
25 Fox H. Pathology of the placenta in maternal diabetes mellitus. Obstet Gynecol 1969;34:792-8.
26 Asmussen I. Ultrastructure of the villi and fetal capillaries of the placentas delivered by non-smoking diabetic women (White group D). Acta Pathol Microbiol Immunol Scand A 1982;90:95-101.
27 Björk O, Persson B. Placental changes in relation to the degree of metabolic control in diabetes mellitus. Placenta 1982;3:367-78.
28 Boyd PA, Scott A, Keeling JW. Quantitative structural studies on placentas from pregnancies complicated by diabetes mellitus. Br J Obstet Gynaecol 1986;93:31-5.
29 Jauniaux E, Burton GJ. Villous histomorphometry and placental bed biopsy investigation in type I diabetic pregnancies. Placenta 2006;27:468-74.
30 Nelson SM, Coan PM, Burton GJ, Lindsay RS. Placental structure in type 1 diabetes: Relation to fetal insulin, leptin, and IGF-I. Diabetes 2009;58:2634-41.
31 Daskalakis G, Marinopoulos S, Krielesi V, Papapanagiotou A, Papantoniou N, Mesogitis S, et al. Placental pathology in women with gestational diabetes. Acta Obstet Gynecol Scand 2008;87:403-7.
32 Madazli R, Tuten A, Calay Z, Uzun H, Uludag S, Ocak V. The incidence of placental abnormalities, maternal and cord plasma malondialdehyde and vascular endothelial growth factor levels in women with gestational diabetes mellitus and nondiabetic controls. Gynecol Obstet Invest 2008;65:227-32.
33 Rudge MV, Lima CP, Damasceno DC, Sinzato YK, Napoli G, Rudge CV, et al. Histopathological placental lesions in mild gestational hyperglycemic and diabetic women. Diabetol Metab Syndr 2011;3:19.
34 Pietro L, Daher S, Rudge MV, Calderon IM, Damasceno DC, Sinzato YK, et al. Vascular endothelial growth factor (VEGF) and VEGF-receptor expression in placenta of hyperglycemic pregnant women. Placenta 2010;31:770-80.
35 Vuorela P, Halmesmäki E. Vascular endothelial growth factor, its receptors, and the tie receptors in the placental bed of women with preeclampsia, diabetes, and intrauterine growth retardation. Am J Perinatol 2006;23:255-63.
36 Cetinkaya B, Ozmen A, Unek G, Bulbul G, Korgun ET. Expressions of vegf, vegfr1, vegfr2 and akt in pregestational diabetic human placentas. Placenta 2014;35:31.
37 Barreiro EG, Pietro L, Mattar R, Damasceno DC, Calderon IM, Rudge MV, et al. Vascular endothelial growth factor (VEGF) in placentas from hyperglycemic pregnant women: Pilot study. J Reprod immunol 2007;75:17.