Pattern of adhesive molecules expression 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.
References (45)
- et al.
Human placenta-derived Wnt-5a induces the expression of ICAM-1 and VCAM-1 in CD133(+)CD34(+)-hematopoietic progenitor cells
Reprod. Biol.
(2014) - et al.
Role of equilibrative adenosine transporters and adenosine receptors as modulators of the human placental endothelium in gestational diabetes mellitus
Placenta
(2013) - et al.
Pre-eclampsia and fetal growth restriction: how morphometrically different is the placenta?
Placenta
(2006) - et al.
Stereological investigation of placental morphology in pregnancies complicated by pre-eclampsia with and without intrauterine growth restriction
Placenta
(2003) - et al.
Endothelial cell expression of adhesion molecules is induced by fetal plasma from pregnancies with umbilical placental vascular disease
BJOG Int. J. Obestet. Gynaecol.
(2002) - et al.
Favorable outcomes of hydroxychloroquine in insulin resistance may be accomplished by adjustment of the endothelial dysfunction as well as the skewed balance of adipokines
Acta Histochem.
(2016) - et al.
ICAM-1 signaling in endothelial cells
Pharmacol. Rep. P. R.
(2009) - et al.
ICAM-1 molecular mechanism and genome wide SNP's association studies
Indian heart J.
(2015) - et al.
Signs of maternal vascular dysfunction precede preeclampsia in women with type 1 diabetes
J. diabetes Complicat.
(2007) - et al.
Altered circulating levels of adhesion molecules at 18 weeks' gestation among women with eventual preeclampsia: indicators of disturbed placentation in absence of evidence of endothelial dysfunction?
Am. J. Obestet. Gynecol.
(2000)
Should we consider gestational diabetes a vascular risk factor?
Atherosclerosis
Placental angiogenic growth factors and uterine artery Doppler findings for characterization of different subsets in preeclampsia and in isolated intrauterine growth restriction
Am. J. Obestet. Gynecol.
Placental villus morphology in relation to maternal hypoxia at high altitude
Placenta
Low target birth weight or growth retardation? Umbilical Doppler flow velocity waveforms and histometric analysis of fetoplacental vascular tree
Am. J. Obestet. Gynecol.
Adhesion molecules expression in the placental bed of pregnancies with pre-eclampsia
BJOG Int. J. Obestet. Gynaecol.
Labour-associated expression of intercellular adhesion molecule-1 (ICAM-1) in placental endothelial cells indicates participation of immunological processes in parturition
Placenta
Microvascular endothelial cell activation is present in the umbilical placental microcirculation in fetal placental vascular disease
Am. J. Obestet. Gynecol.
Features of endothelial dysfunction in umbilical cord vessels of women with gestational diabetes
Nutr. Metabol., Cardiovasc. Dis. NMCD
Glucose, Insulin, Oxyg. Interplay Placent. Hypervascularisation Diabetes Mellitus
Pregnancy outcomes after assisted reproductive technology
J. Obestet. Gynaecol. Can. JOGC = J. Obstet. Gynecol. du Can. JOGC
Altered gene expression in human placentas after IVF/ICSI
Hum. Reprod. (Oxf. Engl.)
Abnormal placentation: evidence-based diagnosis and management of placenta previa, placenta accreta, and vasa previa
Obstet. Gynecol. Surv.
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