Studying in detail different histomorphological and pathological findings in placental stem and terminal villi of appropriate for gestational age (AGA) and idiopathic intrauterine growth restricted (IUGR) fetuses, then analyzing their correlation to the neonatal birth weight and to the some morphological features of the placenta. Fifty full-term human placentae of idiopathic IUGR and 25 of AGA pregnancies were processed for haematoxylin and eosin staining and evaluated by light microscope aided with Image Analyzer. The mean number of stem villous arteries, and the mean number of terminal villous capillaries per field are significantly lower in idiopathic IUGR group (4.63 ± 0.46, 47.09 ± 4.44, respectively) than in AGA group (12.36 ± 0.61, 73.35 ± 5.13, respectively) (p = 0.001). Both AGA and idiopathic IUGR placentae share the presence of many pathological features: (1) narrowing of stem villous arteries appears in 38 (76 %) of IUGR cases and in 9 (36 %) of AGA cases with significant difference between groups (p = 0.001); (2) cellular infiltration (villitis) of the stem villi is significantly higher in IUGR cases [24 (48 %)] than in AGA cases [2 (8 %)] (p = 0.001). The study shows significant correlation between the birth weight and different pathologic features in the stem villi as arterial number (r = 0.494; p = 0.000), arterial narrowing (r = 0.283, p = 0.004), degenerative changes (r = 0.331, p = 0.001) and villitis (r = 0.275, p = 0.005). There is also significant correlation between neonatal birth weight and terminal villous capillary number (r = 0.281, p = 0.001) but no significant correlation is found between the birth weight and terminal villous fibrotic changes (r = -0.098, p = 0.318). Histomorphological and pathological changes in the stem villi could explore the cause of idiopathic IUGR. Stem villous arterial number, arterial narrowing, degeneration and villitis could be underlying mechanisms. Further researches on the hormonal and cytokine level should be undertaken to demonstrate the precipitating factors of these changes and the possible preventing measures.
"FGR affects 4–7% of live births in developed countries and contributes significantly to prematurity, perinatal morbidity, and mortality (Wang et al., 2007). Investigations using random block sampling and stereological studies reported reductions in the number, surface area, and volume of terminal villi in FGR-affected placentae, compared with placentae from uncomplicated pregnancies (Biagiotti et al., 1999; Egbor et al., 2006; Biswas et al., 2008; Vedmedovska et al., 2011; Almasry et al., 2012; Almasry and Elfayomy, 2012). Additionally, villous vessels exhibited fewer branches, and a majority of the vessels were slender and uncoiled (Teasdale, 1984; Teasdale and Jean-Jacques, 1988; Jackson et al., 1995; Chen et al., 2002; Mayhew, 2003; Tomas et al., 2010). "
[Show abstract][Hide abstract] ABSTRACT: Homeobox genes are essential for both the development of the blood and lymphatic vascular systems, as well as for their maintenance in the adult. Homeobox genes comprise an important family of transcription factors, which are characterized by a well conserved DNA binding motif; the homeodomain. The specificity of the homeodomain allows the transcription factor to bind to the promoter regions of batteries of target genes and thereby regulates their expression. Target genes identified for homeodomain proteins have been shown to control fundamental cell processes such as proliferation, differentiation, and apoptosis. We and others have reported that homeobox genes are expressed in the placental vasculature, but our knowledge of their downstream target genes is limited. This review highlights the importance of studying the cellular and molecular mechanisms by which homeobox genes and their downstream targets may regulate important vascular cellular processes such as proliferation, migration, and endothelial tube formation, which are essential for placental vasculogenesis and angiogenesis. A better understanding of the molecular targets of homeobox genes may lead to new therapies for aberrant angiogenesis associated with clinically important pregnancy pathologies, including fetal growth restriction and preeclampsia.
Frontiers in Pharmacology 06/2014; 5:133. DOI:10.3389/fphar.2014.00133 · 3.80 Impact Factor
"Intrauterine growth restriction (IUGR) is a condition characterized by reduced fetal growth, low plasma oxygen (hypoxia) and increased feto-placental vascular resistance [1e3]. Studies have demonstrated that vascularity in IUGR-derived placenta is influenced by a diminished vascular volume and remodeling  , remodeling and impaired response to vasodilator agents . "
[Show abstract][Hide abstract] ABSTRACT: Placental vascular tone is critically influenced by nitric oxide (NO) derived from endothelial NO synthase (eNOS) activity. Placental vessels from pregnancies complicated with intrauterine growth restriction present altered NOS-dependent vasodilation. Arginase-2 competes with eNOS for l-arginine and counteracts the NOS-dependent relaxation in umbilical vessels from normal pregnancies. However there is no data regarding the contribution of arginase activity on the impaired endothelial function in IUGR placenta. We studied whether arginase-2 participates in IUGR-related placental vascular dysfunction counteracting eNOS-dependent relaxation, and the regulation of arginase-2 and eNOS expression in endothelial cells from IUGR umbilical arteries (HUAEC) and veins (HUVEC). In IUGR-derived umbilical arteries (UA) and veins (UV), and chorionic arteries (CA), NOS-dependent vasoactive response in the presence and absence of BEC (arginase inhibitor) was studied. Protein levels of eNOS (total and Ser(1177)-P-eNOS), arginase-2 and arginase activity were determined in IUGR HUAEC and HUVEC. In IUGR vessels eNOS-dependent relaxation was reduced, being improved by BEC. This effect was higher in arteries than veins, and in chorionic compared with umbilical vessels. In cultured IUGR endothelial cells, arginase-2 protein expression and activity were increased in HUVEC, without changes in HUAEC. In IUGR-derived endothelium there was a generalized reduction in the in vitro eNOS activation (Ser(1177)-P-eNOS/eNOS), and therefore a decreased eNOS/arginase activity ratio. Here we provide ex vivo and in vitro evidence for a vascular role of arginase throughout placental vasculature, negatively controlling NOS activity. This effect seems to be crucial in the pathophysiology of endothelial dysfunction present in IUGR feto-placental vessels.
[Show abstract][Hide abstract] ABSTRACT: The placenta acts a regulator of nutrient composition and supply from mother to fetus and is the source of hormonal signals that affect maternal and fetal metabolism. Thus, appropriate development of the placenta is crucial for normal fetal development. We investigated the effect of gestational protein restriction (GPR) on placental morphology and mitochondrial function on day 19 of gestation. Pregnant dams were divided into two groups: normal (NP 17 % casein) or low-protein diet (LP 6 % casein). The placentas were processed for biochemical, histomorphometric and ultrastructural analysis. The integrity of rat placental mitochondria (RPM) isolated by conventional differential centrifugation was measured by oxygen uptake (Clark-type electrode). LP animals presented an increase in adipose tissue and triacylglycerol and a decrease in serum insulin levels. No alterations were observed in body, liver, fetus, or placenta weight. There was also no change in serum glucose, total protein, or lipid content. Gestational protein restriction had tissue-specific respiratory effects, with the observation of a small change in liver respiration (~13 %) and considerable respiratory inhibition in placenta samples (~37 %). The higher oxygen uptake by RPM in the LP groups suggests uncoupling between respiration and oxidative phosphorylation. In addition, ultrastructural analysis of junctional zone giant cells from LP placenta showed a disorganized cytoplasm, with loss of integrity of most organelles and intense vacuolization. The present results led us to hypothesize that GPR alters placental structure and morphology, induces sensitivity to insulin, mitochondrial abnormalities and suggests premature aging of the placenta. Further studies are needed to test this hypothesis.
Tanja Nadine Stüber, Eric Frieauff, Claire Weiß, Ursula Zollner, Achim Wöckel, Thomas Meyer, Monika Rehn
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