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ORIGINAL ARTICLE  
Year : 2012  |  Volume : 55  |  Issue : 1  |  Page : 17-21
Placental morphology in pre-eclampsia and eclampsia and the likely role of NK cells


1 Department of Morbid Anatomy and Histopathology, University of Health Sciences, Khayaban-E-Punjab, Pakistan
2 Department of Obstetrics and Gynaecology, King Edward Medical University, Lahore, Pakistan

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Date of Web Publication11-Apr-2012
 

   Abstract 

Background: Placenta has long been a neglected organ as far as its pathology is concerned. This study is an attempt to observe the morphological features of placentae both gross and microscopic in normal pregnancy, preeclampsia, and eclampsia. Materials and Methods: A total of 150 placentae were collected; of these, 50 belonged to normal pregnancy, 50 belonged to pre-eclamptic women, and 50 were from patients of eclampsia. Results: Placental trimmed weight was seen to be decreased in patients of preeclampsia and eclampsia. Placental infarcts were more commonly seen in the diseased group and they were more centrally located. Hypertrophy of the spiral arterioles was observed in the decidual portion found in placental disc and membranes. Distal villous hypoplasia was also frequently seen in the diseased group. Fetal membranes were thickened and showed infarcts in preeclampsia and eclampsia. Conclusions: Morphological features seen in eclamptic placentae were similar but exaggerated compared to preeclampsia. In conclusion, the pathological changes were found to be more severe and frequent in preeclampsia and eclampsia, but more so in eclamptic placentae as compared with placenta of normal pregnancy. CD56 immunomarker was also used to identify NK cells. They were found to be present only in the diseased group and were located in the decidual portion of the basal plate, implicating their role in the development of the disease.

Keywords: Eclampsia, Natural Killer cell, pre eclampsia, placental infarcts

How to cite this article:
Akhlaq M, Nagi AH, Yousaf AW. Placental morphology in pre-eclampsia and eclampsia and the likely role of NK cells. Indian J Pathol Microbiol 2012;55:17-21

How to cite this URL:
Akhlaq M, Nagi AH, Yousaf AW. Placental morphology in pre-eclampsia and eclampsia and the likely role of NK cells. Indian J Pathol Microbiol [serial online] 2012 [cited 2020 Oct 25];55:17-21. Available from: https://www.ijpmonline.org/text.asp?2012/55/1/17/94848



   Introduction Top


The placenta so far is a poorly understood organ that plays a central role in pregnancy. [1] It has been described as a ''diary of intrauterine life'' and has the potential to elucidate many aspects of the processes going on during pregnancy. [2] Examination of placenta is important for both mother and infant and can yield information which is important for later management of both infant and the mother. [3] Two such disorders are preeclampsia and eclampsia affecting the mother, where placenta plays a fundamental role. The placenta, however, continues to be an underutilized and improperly handled surgical material. [4] Pre-eclampsia is a frequent disorder with a reported incidence of 2-8% among pregnancies. Pre-eclampsia/eclampsia probably accounts for more than 50,000 maternal deaths worldwide each year. [5] Preeclampsia, a major killer of mother and fetus, has traditionally been called the disease of theories; however, research during the past 10 years has changed that concept. Earlier observations have concluded that all the signs and symptoms of this disease resolve after delivery of placenta. Therefore, placenta is a natural focus of the source of this disease. [6] Preeclampsia and eclampsia are multifaceted hypertensive disorder of pregnancy affecting several systems. The nervous system is commonly affected and is a cause of significant morbidity and death in these women. Preeclampsia and eclampsia are not separate disorders, but are differentiated according to their clinical symptoms. [7] Both these disorders are the commonest and most serious diseases of human pregnancy, occurring in mid to late stages of gestation. The diagnosis is made on three clinical signs: Pregnancy induced hypertension, proteinuria, and edema. Severe deterioration is marked by organ dysfunction and development of a convulsive condition when it is called eclampsia. [8] Pre-eclampsia is defined as gestational blood pressure elevation with proteinuria that develops after 20 weeks' of gestation. Criteria for the diagnosis of preeclampsia, therefore, is systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg and proteinuria of 0.3 g or greater in a 24-hour urine specimen. When convulsions also occur, the condition is referred to as eclampsia. [9],[10] In eclampsia, the typical clinical picture is of generalized tonic-clonic seizures during third trimester, during labor, or puerperium in women who already have hypertension, proteinuria, and edema. [11] The etiology and the only known cure for this condition involve the placenta which is essentially an allograft. Its implementation requires an allogenetic recognition system based on natural killer cells rather than T cells. [12] Decidual Natural Killer (NK) cells are usually positive with immunomarker CD56. [13] Some studies suggest that NK cells play an important role in the process of placentation and strip off the muscular wall of the spiral arteries and displace endothelial cells that line these vessels making them low resistance channels. [14] Aberrant NK cell activation may be the cause of preeclampsia, but their exact role is still uncertain. [15] Keeping this in mind, we stained NK cells by using immunohistochemistry technique (IHC) in placentae of preeclampsia, eclampsia, and normal pregnancy. Aim of this study was to observe the pathological morphology of placentae in women presenting with the clinical features of preeclampsia and eclampsia and compare this with the morphology of placentae from normal pregnancy and to discover NK cells in these placenta.


   Materials and Methods Top


Patients/Placentae

A total of 150 placentae were collected, of these, 50 belonged to women diagnosed as preeclampsia, 50 were from mothers diagnosed as eclampsia, and 50 placentae were taken from those who carried normal pregnancy. The study was conducted in the department of morbid anatomy and histopathology at the University of Health Sciences, Lahore. Placentae were collected from pregnant women of all ages and parity. Patients with co-morbid conditions like diabetes mellitus, asthma, and drug dependence were excluded.

Placental Examination

Fresh placentae were preserved in 10% formalin. Following gross features were recorded: Weight of trimmed placentae (without cord and membranes), length of umbilical cord, diameter of placental disc, thickness of placental disc, insertion point of umbilical cord, diameter of umbilical cord, color of umbilical cord, number of vessels in umbilical cord, number of twists per representative 10 cm of length of umbilical cord, presence of true knots and/or pseudo knots in umbilical cord, insertion of membranes and their completeness, thickness of membranes, appearance of chorionic plate, appearance of basal plate, complete presence of cotyledons, examination of serial cut sections, and any added abnormality like infarct, plaques, hematomas etc.

Tissue Processing

Tissues sections were taken from the following areas of each placenta: Two sections from the middle of umbilical cord, two from membrane rolls, two from the placental disc, and additional tissues were taken in case of a visible abnormality.

The tissues taken were processed using ascending grades of ethyle alcohol, xylene, and parrafin wax in an automatic tissue processor. The tissues were embedded in paraffin wax and cut at four micron intervals using a Leica rotary microtome. They were stained with hematoxylin-eosin, MSB, and Masson's trichrome. In addition, the sections from placental disc containing decidual portion were stained for CD56 using immunohistochemistry technique (IHCT) to identify NK cells.

Statistical Analysis

The data was entered and analyzed using Statistical Package for the Social Sciences (SPSS) 17.0 and STATA 8.2. Frequencies and percentages were given for qualitative variables. Pearson Chi-square and Fisher exact test were applied to observe association between qualitative variables. A P value of <0.05 was considered as statistically significant.


   Results Top


Most of the women in the diseased groups fell into a slightly younger age bracket of 18-28 years compared to the normal pregnancy group [Table 1]. A big portion of eclamptic patients was primigravida; however, there was a strong link with the previous history of toxemia of pregnancy and eclampsia. Retarded fetal growth was seen only in the diseased group [Table 2].
Table 1: Maternal clinical features in 150 placentae in all the three groups (n=50 each)

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Table 2: Outcome of pregnancy in 150 placentae in all the three groups

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The placentae of diseased groups were less in weight, size, and in thickness compared to those of normal pregnancy [Table 3] [Figure 1]. Maternal surface infarcts were about three times more common in diseased group [Figure 2]. Red infarcts of placental discs and membrane infarcts were seen only in the diseased groups, whereas white infarcts were observed in both the normal and diseased pregnancy. The microscopical features seen in placentae of the diseased and control groups showed increased syncytial knots which increased with gestational age [Figure 3]. Microscopic necrosis of villi, seen as ghost villi surrounded by fibrin, is more frequent in diseased groups [Figure 4]. Perivillous fibrin and syncytial knots were scored by an arbitrary scoring system by counting the number at x10 magnification. Three + was given to greater than six perivillous fibrin deposits and 15-20 syncytial knots. Necrosis of placental discs was present in twice the number of placentae of diseased groups as compared to controls. Smooth muscle hypertrophy of spiral arterioles and distal villous hypoplasia were all increased in diseased group [Table 4]. Decidual NK cells, stained using CD56 immunomarker, were expressed only in the diseased group [Figure 5]. Membrane staining was considered positive and arbitrary scoring at 10x was carried out as follows: 1-10 cells = +, 11-20 cells = + +, >20 cells = + + +.
Figure 1: A difference in the size of normal (left) and pre-eclamptic placentae (right)

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Figure 2: Cross sections of an eclamptic placenta showing multiple pale and red infarcts

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Figure 3: ++++ syncytial knots (MSB stain) × 200

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Figure 4: Necrosis of villi (Masson's Trichrome stain) × 40

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Figure 5: Membranous CD56 staining of NK cells (3+) in the decidua of basal plate × 40

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Table 3: Gross morphology in 150 placentae in all the three groups

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Table 4: Microscopic features of 150 placentae in three groups

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   Discussion Top


In the present study, the commonest age range of the mothers in preeclampsia and eclampsia was 24-28 years and the age range of 18-23 years was the next common group. This is supported by another study reporting similar results in hypertensive pregnant women. [16] On the other hand, a study carried out in Ghana showed that pre-eclampsia occurred significantly more in women above 35 years and below 20 years of age. [17] There was a trend towards higher rates of pre-term delivery (< 37weeks), caesarean section, small for gestational age babies, stillbirth, and lower baby birth weight (<2.0 k g) compared to the normal pregnancy group. This is similar to other reports. [18],[19] Patients of both pre-eclampsia and eclampsia can be associated with positive family history that was statistically significant. [20]

The maximum number of pre-eclamptic placentae in the present study showed thickness of 1.5-2.0 cm that was similar to a Bangladeshi study. [21] The placental weight in our cases of pre-eclampsia and eclampsia was less than the normal range of 500 g. This is supported by a Turkish study. [22] In the present study, placental white infarcts were common in pre-eclampsia and eclampsia (52% and 62%, respectively) and small white infarcts were found in 12% of placentae of normal pregnancy which is comparable to a study by Salgado and Pathmeswaran [16] in 2008, showing that 30% placentae from hypertensive group had white infarcts and were also found in 18% of normal pregnancy placentae. Placental red infarcts were commonly seen in preeclampsia and eclampsia in our study (20% and 34%, respectively), and were absent in placentae of normal pregnancy. This finding is similar to the study by Robert and Post. [23] Decidual arteriopathy results in reduction of the blood flow to the placental villus that in turn leads to distal villous hypoplasia. It was observed in the diseased group as statistically significant and was similar to that reported by Roberts and Post. [23] Increased syncytial knots formed by an imbalance between the productions and shedding of villous syncytiotrophoblast were also observed in the present study and were seen statistically significant in number in the diseased placentae. It has been suggested that syncytial knots increase with increasing gestational age and may be used to evaluate villous maturity. [24]

We also stained NK cells using immunostaining on the paraffin embedded blocks of placentae for the first time in this study. Previously, only one such study was reported using CD56 for the staining of NK cells in frozen sections of placentae from pre-eclamptic patients. [13] We, however, stained the tissue sections for CD56 to identify NK cells using formalin fixed paraffin embedded tissue. The stain was taken up very well using IHC technique. Our results were similar to those of Bachmayer et al. [13] According to our observation, NK cells were found to be increased in pre-eclamptic and eclemptic placentae. It suggested that NK cell functions and interactions with fetal-derived trophoblasts have a profound impact on outcome of pregnancy. Altered NK cell numbers and activity have been associated with recurrent pregnancy loss and pre-eclampsia. It is also suggested that uterine NK cells can produce cytokines that may be an important part of vascular remodeling during placental development. [25]

Although, at present, we do not know the exact cause and effect relationship between NK cells and the occurrence of pre-eclampsia and eclampsia, it is suggested that NK cells resist the invasion of maternal vessels by trophoblasts and thus contribute to the development of vascular resistance and decreased perfusion of placenta leading to pre-eclampsia and eclampsia. NK cells act as an innate immune defense against the paternal antigens of the fetus. Further work is needed to be done on the in depth role of NK cells in pregnancy.


   Conclusion Top


It is concluded that important findings in placentae of pre-eclampsia and eclampsia is the presence of red infarcts and decreased placental weight on gross examination. Microscopic examination reveals distal villous hypoplasia, villous necrosis, and decidual arterial hypertrophy are common and significant findings. NK cells were observed in the decidual portion of the maternal surface of the placentae of pre-eclampsia and eclampsia. This may implicate their role in the pathogenesis of these two diseases.

 
   References Top

1.Desoye G, Kaufman P. The human placenta in diabetes. In: Djelmis J, Desoye G, Ivasinevic M, editors. Diabetology of Pregnancy (Frontiers in Diabetes). Vol. 17. Switzerland: Basel, Karger; 2005. p. 94-109.   Back to cited text no. 1
    
2. Redline RW. Placental Pathology: A systematic approach with clinical correlations. Placenta 2008;29:86-91.  Back to cited text no. 2
    
3.American family physician. Kansas: American Academy of Family Physicians. In: Yetter JF, editor. Examination of the placenta [Last updated on 1998 Mar 01] Available from: http://www.aafp.org/afp/980301ap/yetter.html [Last cited on 2008 Sep 13].  Back to cited text no. 3
    
4.Roberts DJ. Placental Pathology: A survival guide. Arch Pathol Lab Med 2008;132:641-51.  Back to cited text no. 4
    
5.Genev Foundation of Medical Education and research. Switzerland. In: Sahin G, Gulmezoglu M, editors. Incidence: Morbidity and mortality of pre-eclampsia and eclampsia 2003. [Last updated on 2008 Sep 04]. Available from: http://www.gfmer.ch/Endo/Course2003/Eclampsia.htm. [Last cited on 2008 Nov 13].  Back to cited text no. 5
    
6.Karumanchi SA, Lindheimer MD. Preeclampsia Pathogensis: "Triple A Rating"- autoantibodies and antoangiobenic factors. Hypertension 2008;51:991-2.  Back to cited text no. 6
    
7.Emedicine.medscope.com. Shah AK, editor. Preeclampsia and Eclampsia [Last updated on 2009 Jan 18] Available form: http://www.emedicine.medscope.com/article/118420-overview. [ Last cited on 2009 June 18].   Back to cited text no. 7
    
8. Guo G, Lade JA, Wilton AN, Moses EK, Grehan M, Qiu YF, et al. Genetic susceptibility to preeclampsia and chromosome 7q36. Hum Genet 1999;105:641-7.  Back to cited text no. 8
    
9.Emedicine.mescope.com. Campbell DE, editor. Preeclampsia [Last updated on 2009 Jan 06] Available from: http://www.emedicine.medscope.com/article/953579-overview. [Last cited on 2009 June 18].  Back to cited text no. 9
    
10.Subramaniam, V. Seasonal variation in the incidence of preeclampsia and eclampsia in tropical climatic conditions. BMC Women's Health 2007;7:1-18.  Back to cited text no. 10
    
11.Munjuluri N , Lipman M , Valentine A , Hardiman P, Maclean AB. Postpartum eclampsia of late onset. BMJ 2005;331:1070-1.  Back to cited text no. 11
    
12.Blum A, Shenhav M, Baruch R, Hofmann M. Endothelial dysfunction in preeclampsia and eclampsia: Current etiology and future non-invasive assessment. Isr Med Assoc J 2003;5:724-6.  Back to cited text no. 12
    
13.Bachmayer N, Rafiq HR, Liszka L, Bremme K, Sverremark-Ekstim E. Aberrant uterine natural killer (NK)-cell expression and altered placental and serum levels of the NK-cell promoting cytokine interleukin-12 in pre-eclampsia. Am J Reprod Immunol 2006;56:292-301.  Back to cited text no. 13
    
14.Parham P. NK Cells and trophoblasts: Partners in pregnancy. J Exp Med 2004;200:951-5.  Back to cited text no. 14
    
15.Sergesnt IL, Borzychowski AM, Redman CW. NK Cells and preeclampsia. J Reprod Immunol 2007;76:40-4.   Back to cited text no. 15
    
16. Salgado SS, Pathmeswaran A. Effects of placental infarctions on the fetal outcome in pregnancies complicated by hypertension. J Coll Physicians Surg Pak 2008;18:213-6.  Back to cited text no. 16
    
17.Obed SA, Patience A. Birth weight and ponderal index in pre-eclampsia: A comparative study. Ghana Med J 2006;40:8-13.  Back to cited text no. 17
    
18.Lydakis C, Beevers M, Beevers DG, Lip GY. The prevalence of pre-eclampsia and obstetric outcome in pregnancies of normotensive and hypertensive women attending a hospital specialist clinic. Int J Clin Pract 2001;55:361-7.  Back to cited text no. 18
    
19.Noor S, Halimi M, Faiz, NR, Gull F, Akbar N. Magnesium Sulphate in the prophylaxis and treatment of eclampsia. J Ayub Med Coll Abottabad 2001;16: 12-5.  Back to cited text no. 19
    
20.Duckitt K, Harrington D. Risk factors for preeclampsia at antenatal booking: Systemic review of controlled studies. BMJ 2005;330:565-9.  Back to cited text no. 20
    
21.Kishwara S, Shamim A, Rayhan KA, Begum M. Morphological changes of placenta in preeclampsia. Bangladesh J Anat 2009;7:49-54.  Back to cited text no. 21
    
22.Saleh RA, Dkhil MA. Structural changes of placenta in preeclamptic patients: Light and electron microscopic study. Turk J Med Sci 2008;38:219-25.  Back to cited text no. 22
    
23.Roberts DJ, Post MD. The placenta in preeclampsia and IUGR. J Clin Pathol 2008;61:1254-60.  Back to cited text no. 23
    
24.Loukeris K, Sela R, Baergen R. Syncytial knots as a reflection of placental maturity: Reference values for 20 to 40 weeks gestational age. Pediatr Dev Pathol 2010;13:305-9.  Back to cited text no. 24
    
25.Drake PM, Gunn MD, Charo IF, Tsou CL, Zhou Y, Huang L, et al. Human placental cytotrophoblasts attract monocytes and CD 56 bright natural killer cells via the actions of monocyte inflammatory protein 1α. J. Exp. Med 2001;193:1199-212.  Back to cited text no. 25
    

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Correspondence Address:
Maham Akhlaq
12 Saxon Green, Lenton, Nottingham, NG72LL, UK

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.94848

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]

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