Intrauterine growth restriction and placental angiogenesis

Barut, Figen; Barut, Aykut; Gün, Banu Doğan; Kandemır, Nilüfer Onak; Harma, Mehmet; Harma, Müge; Aktunç, Erol; Özdamar, Şükrü Oğuz

doi:10.1186/1746-1596-5-24

Cited by 113 publications

(109 citation statements)

References 20 publications

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“…Defects in placental vascular development can cause embryonic death and abnormal organogenesis, can negatively affect fetal growth and can confer a higher risk of disease in the postnatal life (Barker et al, 1989). For example, defective patterning of the fetoplacental vasculature, also known as the labyrinth, results in abnormal heart development in mouse (Shaut et al, 2008) and human (Demicheva and Crispi, 2014), and causes intrauterine growth restriction (IUGR) (Barut et al, 2010). IUGR affects up to 32% of pregnancies in some developing countries (Ananth and Vintzileos, 2009), and can cause cardiovascular disease in utero and in adulthood (Demicheva and Crispi, 2014).…”

Section: Introductionmentioning

confidence: 99%

Ehmt2/G9a controls placental vascular maturation by activating the Notch pathway

et al. 2017

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Defective fetoplacental vascular maturation causes intrauterine growth restriction (IUGR). A transcriptional switch initiates placental maturation where blood vessels elongate. However, cellular mechanisms and regulatory pathways involved are unknown. We show that the histone methyltransferase Ehmt2, also known as G9a, activates the Notch pathway to promote placental vascular maturation. Placental vasculature from embryos with G9a-deficient endothelial progenitor cells failed to expand due to decreased endothelial cell proliferation and increased trophoblast proliferation. Moreover, G9a deficiency altered the transcriptional switch initiating placental maturation and caused downregulation of Notch pathway effectors including Rbpj. Importantly, Notch pathway activation in G9a-deficient endothelial progenitors extended embryonic life and rescued placental vascular expansion. Thus, G9a activates the Notch pathway to balance endothelial cell and trophoblast proliferation and coordinates the transcriptional switch controlling placental vascular maturation. Accordingly, G9A and RBPJ were downregulated in human placentae from IUGR-affected pregnancies, suggesting that G9a is an important regulator in placental diseases caused by defective vascular maturation.

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Section: Introductionmentioning

confidence: 99%

Ehmt2/G9a controls placental vascular maturation by activating the Notch pathway

et al. 2017

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“…Interestingly, in vitro studies showed that IUGR placental villous stromal cells altered ability to stimulate endothelial tubule-like structure formation and migration [37]. In addition, the imbalance between pro-and antiangiogenic factors is well documented in placentas and in maternal blood of IUGR and PE pregnancies, suggesting a role in their pathophysiology [38,39]. Endothelial progenitors contribute to tissue regeneration by induction of new vessels, thereby increasing tissue perfusion and oxygenation [40,41].…”

Section: Discussionmentioning

confidence: 99%

Impaired Angiogenic Potential of Human Placental Mesenchymal Stromal Cells in Intrauterine Growth Restriction

Mandò

Razini

Novielli

et al. 2016

Stem Cells Translational Medicine

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Human placental mesenchymal stromal cells (pMSCs) have never been investigated in intrauterine growth restriction (IUGR). We characterized cells isolated from placental membranes and the basal disc of six IUGR and five physiological placentas. Cell viability and proliferation were assessed every 7 days during a 6-week culture. Expression of hematopoietic, stem, endothelial, and mesenchymal markers was evaluated by flow cytometry. We characterized the multipotency of pMSCs and the expression of genes involved in mitochondrial content and function. Cell viability was high in all samples, and proliferation rate was lower in IUGR compared with control cells. All samples presented a starting heterogeneous population, shifting during culture toward homogeneity for mesenchymal markers and occurring earlier in IUGR than in controls. In vitro multipotency of IUGR-derived pMSCs was restricted because their capacity for adipocyte differentiation was increased, whereas their ability to differentiate toward endothelial cell lineage was decreased. Mitochondrial content and function were higher in IUGR pMSCs than controls, possibly indicating a shift from anaerobic to aerobic metabolism, with the loss of the metabolic characteristics that are typical of undifferentiated multipotent cells.

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“…Any alteration of capillaries in terminal villi has straight effect on fetomaternal transfusion, fetal growth and development [5]. Development of fetus could be disturbed by placental insufficiency that can result to low birth weight, premature infants, and increased perinatal mortality and morbidity [6][7][8][9]. Placental size and microvessels' quantity increase up to the end of the pregnancy as fetal nutrients requirements increase with gestational duration [1,10].…”

Section: Introductionmentioning

confidence: 99%

Correlations of morphometric placental microvessels parameters with birth weight.

Boruah

Mohanlal

Malik

et al. 2017

AAMS

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Introduction: Birth weight (BWT) is greatly affected by placental insufficiency and the microvessels configurations. Aims of this study were to evaluate various parameters: villous density (VD), microvessel density (MVD), microvessels per villus (MVPV), mean microvessel caliber (VC), total microvessels boundary density (TVBD), maximum possible total length of microvessels (MP-TVL) and maximum possible total surface area of microvessels (MP-TVSA) in terminal villi of placenta. All the parameters including placental weight (PWT) were correlated with BWT; and MVD and VC of placenta were compared with the human tissues from various lesions. Materials and methods:Sixty human placentas of uncomplicated term pregnancies (≥37weeks) managed at this tertiary care institute were included. Formalin fixed paraffin embedded sections of placental tissues were used for computer assisted digital image morphometry. H&E stained sections were used to determine VD and CD34 immuno-stained sections were used for evaluation of vascular parameters in terminal villi. Results: The mean VD was 204 mm-2, the mean MVD was 1314 mm-2, the mean MVPV was 6.6, the mean MVC was 10.15 µm, the mean TVBD was 40.64 mm-1, the mean MP-TVL was 626 km and the mean MP-TVSA was 19.23 m2. The BWT showed significant (p<0.05) positive correlations with PWT (r=0.690), VD (r=0.328), MVD (r=0.408), TVBD (r=0.280), MP-TVL (r=0.723) and MP-TVSA (r=0.723); whereas did not show significant correlations with MVPV (r=0.185, p=0.157) and VC (r=-0.249, p=0.054). MVD in placentas showed strong negative correlation with VC (r=-0.712). MVD in placentas were several times (~ 6.3 times) higher than human tissues; though mean caliber of microvessels in placenta was comparable. Conclusion:PWT, VD, MVD and TVBD in placenta showed significant positive correlations with BWT. Estimated MP-TVL and MP-TSA showed the best correlations with BWT. Placental MVD showed strong negative correlation with VC. Total length of microvessels in the placenta was comparable to that estimated for the fetus. Keywords: Microvessels in

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Intrauterine growth restriction and placental angiogenesis

Cited by 113 publications

References 20 publications

Ehmt2/G9a controls placental vascular maturation by activating the Notch pathway

Ehmt2/G9a controls placental vascular maturation by activating the Notch pathway

Impaired Angiogenic Potential of Human Placental Mesenchymal Stromal Cells in Intrauterine Growth Restriction

Correlations of morphometric placental microvessels parameters with birth weight.

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