Elsevier

Placenta

Volume 48, December 2016, Pages 126-132
Placenta

Pattern of adhesive molecules expression in placenta of non-complicated ART pregnancies

https://doi.org/10.1016/j.placenta.2016.10.016Get rights and content

Highlights

  • No obvious changes are detected in the histological structure of placentas of ART pregnancies.

  • They show a significant decrease in the syncytiotrophoblast cytoplasmic area.

  • They show a significant increase in the vessel area and syncytiotrophoblast nuclear area.

  • No remarkable change in the total villous area and total syncytiotrophoblast % area are detected.

  • Almost all levels of ICAM-1, VCAM-1 and PECAM-1 are increased in placenta as well as in fetal plasma of ART pregnancies.

Abstract

Objective

To investigate changes occurring in the morphometric parameters of chorionic villi and their vessels as well as in adhesive molecules expression in placenta of ART pregnancies.

Methods

Case-control study including a total of 52 placentas of non-complicated pregnancies of women delivered by spontaneous conception (SC) (n = 26) compared with those of ART (n = 26). Histological and morphometric assessment of fetal chorionic villi as well as the expression of various adhesive molecules (ICAM-1, VCAM-1 and PECAM-1) were performed in fetal plasma and placenta.

Results

Although we did not observe any obvious changes in the histological structure of placenta of ART pregnancies, it showed a significant (p < 0.05) decrease in the syncytiotrophoblast cytoplasmic area accompanied with a significant increase (p < 0.05) in the vessel area and syncytiotrophoblast nuclear area without remarkable change in the total villous area or total syncytiotrophoblast % area. In addition, almost all levels of the assayed adhesive molecules were significantly increased (p < 0.05) in placenta as well as in fetal plasma of ART pregnancies compared with SC.

Conclusion

We suggested in the current study that the altered adhesive molecules expression accompanying the increased vessel area and decreased syncytial cytoplasm area may indicate a subclinical endothelial stress in placenta of non-complicated ART pregnancies.

Introduction

The expanding placental vasculature during pregnancy is essential for fetal development. In addition, hypoxia stimulates expression of angiogenic factors that promote angiogenesis and vascular growth [1], [2].

While assisted reproduction technology (ART) is increasingly performed, placenta-related problems as well as obstetrical and perinatal adverse outcomes may occur more frequently than following spontaneous conception (SC) [3], [4]. Moreover, ART pregnancies may increase risk for placenta previa, placenta accreta, and vasa previa [5].

Placental adaptations in ART pregnancies can affect gestational physiology and fetal development as well as long-term patterns of gene expression [4]. In addition, de Waal et al. [6] mentioned that ART procedures increase placental morphological abnormalities and epigenetic perturbations which may modify placental growth and vascularization, potentially leading to adverse pregnancy outcomes and long-term health hazards in the offspring. Therefore, understanding changes occurring in feto-placental vasculature is essential to prevent these hazards [7].

Placental villous and vascular morphology is affected in well-known hypoxic conditions such as pre-eclampsia (PE) and intrauterine growth restriction (IUGR) which may impair placental function and fetal growth by the resultant hypoxic stress [8], [9]. Although ART placentas have normal major histological features, they may display increased thickness, frequent hematomas, ultrastructural degenerative trophoblastic alterations and abnormal placental barrier [10], [11].

Moreover, fetal endothelium dysfunction has a profound impact on fetal development [12]. Endothelial dysfunction occurs in the pathogenesis of micro- and macro-angiopathy of type I and II diabetes mellitus (T1DM, T2DM) [13] and in gestational diabetes (GDM) resulting in functional changes in the placenta and impairment of fetal development [7], [12]. Moreover, feto-placental endothelial dysfunction may be associated with placental morphological changes, however its exact mechanism is not clearly elucidated [14], [15].

Furthermore, expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1), is a feature of endothelial cell activation and microvascular stress [16], [17]. Upregulation of these molecules in endothelial dysfunction promotes migration of leukocytes and activates inflammatory pathways [15], [18], [19]. Their expression is regulated by placental stromal cells and trophoblasts [2].

The circulating maternal s-ICAM-1 and s-VCAM-1 levels vary minimally in uncomplicated pregnancies [20], nevertheless they become elevated in maternal vascular dysfunction and precede development of PE in women with T1DM [21]. Decreased serum s-VCAM-1 and increased s-ICAM-1 levels, may indicate impaired placentation associated with the development of PE [22]. While higher values of ICAM-1 in post-GDM women are consistent with an increased future cardiovascular risk, higher VCAM-1 levels indicate a state of endothelial dysfunction observed in PE and IUGR [23], [24].

In the current study, we investigated the expression of these molecules is in fetal placenta and circulation of non-complicated ART pregnancies and the possible accompanying histological and vascular changes.

Section snippets

Subjects

Placentas were collected immediately after delivery from women with non-complicated pregnancies classified into two groups (Table 1); SC (n = 26), and ART (ICSI) (n = 26) attended at Department of Obstetrics and Gynecology, Mansoura University and Elzeraeen Hospitals between January 2015 and August 2016. Informed written consent was obtained from all included cases for approval of conducting the study by the Ethical Committee of the Faculty of Medicine, Mansoura University.

Patients (≤35 yrs,

Histological and morphometric analysis results

The histological examination of the chorionic villi of the placenta did not reveal any obvious changes between the ART placenta and the SC one. On the other hand, by morphometric analysis a small but significant increase (p < 0.05) in the vessel area was denoted in the chorionic villi of the placenta of ART compared with that of the SC group. Meanwhile, no detectable changes either in the capillary or villous diameter were denoted between placentas of the 2 groups (Fig. 1c). In addition, a

Discussion

ART may promote measurable alterations to intrauterine growth trajectory and placental function, however BW is not a reliable indicator of fetal stress [30]. In addition, placental vascularization and expression of angiogenic factors may be altered in ART pregnancies [31]. Although the great majority of ART children are healthy, many reports suggest a forthcoming risk of adult cardiometabolic diseases [30].

In the current study, histological examination of the chorionic villi did not reveal any

Conclusion

It could be concluded that there may be an element of fetal endothelial stress in the placenta of ART pregnancies evidenced by the elevated levels of almost all adhesion molecules (at mRNA and protein levels) as well as increased chorionic vascular area although most of the placental macro- and micro-scopic features were not significantly altered. These findings may provide an evidence for subclinical feto-placental hypoxia in ART pregnancies which might be hazardous in the long term even with

Conflict of interest

There is no conflict of interest.

Acknowledgements

The authors have not made any acknowledgments.

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