Evidence, evolution and pattern of contractile elements in villous vascular walls and stroma of human placentas of premature infants of different gestational ages. An immuno-morphologic comparative study

The contractile elements of the human placenta villous tree represent a topic of interest and many issues persist still open. Histology of the stroma and muscular wall and their evolution, in relation with the gestational age, remains to be clarified for a deeper understanding of the adaptive potential and pathogenetic mechanisms.In our study, 56 premature placentas (21-36 wks) were considered, sub-divided into four groups based on age of gestation and compared to 23 at-term placentas (37-40 wks). All cases were tested with anti-smooth muscle actin (SMA) and anti-desmin antibodies to identify the contractile elements in the stroma and in vascular walls of villi.SMA and desmin staining show evident decreased expressions during the pregnancy (temporal variation) and from proximal to distal part of the villous tree (spatial variation) being higher in the stem villi.Both pre-term and at-term placentas showed persisting, although variable, positivity for SMA and desmin staining in the stroma and in the vessel walls of the mature intermediate and terminal villi. This represents an unexpected finding and nothing alike has been previously reported in literature.Both highly premature and term placentas seem to maintain contractile components within each type of villi, represented by both myofibroblasts and mature smooth muscular cells. These components may be present in both villous vascular walls and stroma, albeit with different staining intensity.This finding allows us to imagine an active function in the regulation of the blood flow, not only in stem and intermediate immature villi but even in smaller villi.

Accuracy of antepartum ultrasound in evaluating placental pathology using superb microvascular imaging: main research article

Objectives: To clarify whether microvascular ultrasound Doppler (SMI: superb microvascular imaging) can detect antenatal histological findings in pathologic placentas. Methods: In this prospective diagnostic observational study (STROBE), pregnant women who were admitted to our perinatal center for perinatal management were enrolled. Ultrasound examinations to identify placental pathologies using SMI were performed before delivery. After delivery, the placental tissue was clipped for microscopic examination, as the location of the placenta obtained ultrasound findings. The accuracy of antenatal ultrasound detection of placental pathologies was compared between women who were admitted due to fetal growth restriction (FGR), pre-eclampsia, and other indications. Results: The highest accuracy was observed with placental infarction in FGR (positive predictive value [PPV], 100%; sensitivity, 89%; area under the curve [AUC], 0.945), whereas PPV, sensitivity, and AUC in cases of preeclampsia were relatively low (AUC 0.540). Additionally, PPV, sensitivity, and AUC for avascular villi were 100%, 57%, and 0.785 in cases with FGR, 67%, 67%, and 0.780 in cases with preeclampsia, and 80%, 80%, and 0.920, respectively. The diagnostic accuracies predictive of congestion of stem villi and chorangiosis were insufficient (AUC<0.700). Conclusions: SMI can accurately detect placental pathologic findings, such as placental infarction and avascular villi. This modality may improve the perinatal management in cases of placental abnormalities.

Placental Mesenchymal Dysplasia: Ultrasound Characteristics and Diagnostic Pitfalls

Placental mesenchymal dysplasia (PMD) is a rare, benign developmental anomaly with a reported prevalence of 0.02% (Arizawa and Nakayama, 2002). It is characterized by placentomegaly with multiple cystic lesions of the stem villi and vascular anomalies (Pawoo and Heller, 2014). Early detection of PMD has been described during routine prenatal ultrasound (Vaisbuch et al., 2009). The sonographic characteristics of PMD include increased placental thickness and multiple cystic areas within the placenta with either an absence of blood flow or with low venous Doppler signals (Vaisbuch et al., 2009). The differential diagnosis of multicystic placental lesions with the presence of a live fetus include partial molar pregnancy, multiple hematomas, chorioangioma Beckwith-Wiedemann syndrome and PMD. Chorioangiomas are well circumscribed masses within the placenta and they are characterized by the presence of a single feeding vessel with the same pulse rate as the umbilical cord (Zalel et al., 2002). Invasive prenatal testing is required for the exclusion of partial molar pregnancy and Beckwith-Wiedemann Syndrome (Vaisbuch et al., 2009). Definitive diagnosis of PMD is based on the pathologic examination of the placenta. Histology reveals aneurysm or dilated blood vessels that may be thrombosed. The stem villi are edematous and enlarged with thick-walled vessels, without trophoblastic proliferation (Pawoo and Heller, 2014). This case report highlights the significance of the early detection of PMD, illustrates the pitfalls in differential diagnosis and provides valuable insights regarding PMD management in a clinical setting.

TGF-β in fibrosis by acting as a conductor for contractile properties of myofibroblasts

Myofibroblasts are non-muscle contractile cells that play a key physiologically role in organs such as the stem villi of the human placenta during physiological pregnancy. They are able to contract and relax in response to changes in the volume of the intervillous chamber. Myofibroblasts have also been observed in several diseases and are involved in wound healing and the fibrotic processes affecting several organs, such as the liver, lungs, kidneys and heart. During the fibrotic process, tissue retraction rather than contraction is correlated with collagen synthesis in the extracellular matrix, leading to irreversible fibrosis and, finally, apoptosis of myofibroblasts. The molecular motor of myofibroblasts is the non-muscle type IIA and B myosin (NMMIIA and NMMIIB). Fibroblast differentiation into myofibroblasts is largely governed by the transforming growth factor-β1 (TGF-β1). This system controls the canonical WNT/β-catenin pathway in a positive manner, and PPARγ in a negative manner. The WNT/β-catenin pathway promotes fibrosis, while PPARγ prevents it. This review focuses on the contractile properties of myofibroblasts and the conductor, TGF-β1, which together control the opposing interplay between PPARγ and the canonical WNT/β-catenin pathway.

Placental apoptosis in pre-eclampsia

The objective was to determine the presence and severity of placental apoptosis in pre-eclampsia. The study included 31 patients. All patients were divided into 2 groups: group I (treatment) included 11 pregnant women with preeclampsia, group II (control) - 20 healthy patients. Gene expression was evaluated with qPCR assay, and placental apoptosis was assessed by the TUNEL method. It was found that the level of placental apoptosis in preeclampsia patients was significantly higher compared to that of apparently healthy females, and in some cases stem villi are destroyed due to programmed cell death in the villous stroma and syncytiotrophoblast. In preeclampsia, oxidative stress leads to increased levels of apoptosis in placental villi. Both trophoblast cells and, in certain cases, cells of the villous stroma are subject to apoptosis.

EXERCISE EFFECT ON PLACENTAL COMPONENTS: SYSTEMATIC REVIEW AND META-ANALYSIS

Physical exercise has been demonstrated a positive effect on many pregnancy outcomes. Placental components are important for exchanging oxygen and nutrients between mother and fetus. This study aimed to systematic review and meta-analysis whether physical exercise could induce a morphological adjustment on placenta components. We systematically searched PubMed database until October 30th, 2014. We included randomized and non-randomized studies with control group, which aimed to investigate the effect of the physical exercise (water, aerobic and resistance) on placental components (placental weight and volume, villous volume and vascular volume, intervillous space and stem villi). Initially, we identified 222 articles, of which 9 articles were used for full text analysis. Finally, four articles were included in the systematic review and meta-analysis. Meta-analysis demonstrated that exercise appeared to affect placental weight (95% CI, 39.73g [4.66-74.80]), placental volume (95% CI, 47.11 cm3 [37.99-56.23]), intervillous space (95% CI, 16.76 cm3 [12.66-20.68]), villous volume (95% CI, 46.01 cm3 [40.21-51.81]), villous vascular volume (95% CI, 15.95 cm3 [7.83-24.07]) and stem villi (95% CI, 6.00 cm3[4.25-7.75]). Apparently, physical exercise has a positive effect on placental components. However, this conclusion is based on a limited number of studies. Clearly, it stands the necessity of larger samples and better methodology quality.