How to study placental vascular development?

Herr, F.; Baal, Nelli; Widmer-Teske, Rebecca; McKinnon, Timothy; Zygmunt, Marek

doi:10.1016/j.theriogenology.2009.11.003

Cited by 24 publications

(14 citation statements)

References 54 publications

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“…Successful placental development requires proper remodeling of the spiral arteries to allow for unhindered blood flow to the placenta [2,45]. During arterial remodeling, EVT cells acquire a phenotype that mimics cells of the vascular system, particularly endothelial cells [46].…”

Section: Discussionmentioning

confidence: 99%

Mechanisms in Decorin Regulation of Vascular Endothelial Growth Factor-Induced Human Trophoblast Migration and Acquisition of Endothelial Phenotype1

Lala

Girish

Cloutier-Bosworth

et al. 2012

Biology of Reproduction

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Extravillous trophoblast (EVT) cells of the human placenta invade the uterine decidua and utero-placental arteries to establish an efficient exchange of key molecules between maternal and fetal blood. Trophoblast invasion is stringently regulated in situ both positively and negatively by a variety of factors at the fetal-maternal interface to maintain a healthy utero-placental homeostasis. One such factor, decorin, a transforming growth factor (TGF)-beta binding, leucine-rich proteoglycan produced by the decidua, negatively regulates EVT proliferation, migration, and invasiveness independent of TGF-beta. We reported that these decorin actions were mediated by its binding to multiple tyrosine kinase receptors, including vascular endothelial growth factor receptor (VEGFR)-2. The present study explores the mechanisms underlying decorin antagonism of VEGF (VEGF-A) stimulation of endovascular differentiation of EVT using our EVT cell line, HTR-8/SVneo. We observe that decorin inhibits VEGF-induced EVT cell migration and endothelial-like tube formation on matrigel. VEGF activates MAPKs (p38 MAPK, MEK3/6, and ERK1/2) in EVT cells, and the activation is blocked in both cases by decorin. Employing selective MAPK inhibitors, we show that both p38 and ERK pathways contribute independently to VEGF-induced EVT migration and capillary-like tube formation. VEGF upregulates the vascular endothelial (VE) markers VE-cadherin and beta-catenin in EVT and endothelial cells, and this upregulation is blocked by decorin and MAPK inhibitors. These results suggest that decorin inhibits VEGF-A stimulation of trophoblast migration and endovascular differentiation by interfering with p38 MAPK and ERK1/2 activation. Thus decorin-mediated dual impediment of endovascular differentiation of the EVT and angiogenesis may have implications for pathogenesis of preeclampsia, a hypoinvasive trophoblast disorder in pregnancy.

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Section: Discussionmentioning

confidence: 99%

Mechanisms in Decorin Regulation of Vascular Endothelial Growth Factor-Induced Human Trophoblast Migration and Acquisition of Endothelial Phenotype1

Lala

Girish

Cloutier-Bosworth

et al. 2012

Biology of Reproduction

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“…Trophoblast and stromal cells were isolated using anti-CD326 antibody-conjugated magnetic microbeads and MACS system. Anti-CD326 has been established as a specific membrane-bound cell marker [21,22], and it is essential for placental development in mice [23]. The positive fraction (CD326 + cells) consists of trophoblast cells and the negative fraction (CD326 À cells) consists of stromal cells.…”

Section: 2mentioning

confidence: 99%

Human placenta-derived Wnt-5a induces the expression of ICAM-1 and VCAM-1 in CD133+CD34+-hematopoietic progenitor cells

Herr

Horndasch

Howe

et al. 2014

Reproductive Biology

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“…As the causes of IUGR are myriad, IUGR is thought to encompass a broad spectrum of diseases that results from poor nutrient provision to the fetus. This adverse intrauterine environment may, in some cases, result from disordered placentation or poor maternal health and nutrition [1,2]. It is critical to understand the contribution of maternal diet towards the pathophysiology of IUGR, as IUGR not only places offspring of these pregnancies at increased risk of short-term morbidity, but also at increased risk for adult-onset cardiovascular and metabolic diseases [3-6].…”

Section: Introductionmentioning

confidence: 99%

Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction

Chu¹,

Thamotharan²,

Ganguly³

et al. 2016

Nutrition Research

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Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies and often results in short- and long- term sequelae for offspring. The mechanisms underlying IUGR are poorly understood, but it is known that healthy placentation is essential for nutrient provision to fuel fetal growth, and is regulated by immunologic inputs. We hypothesized that in pregnancy, maternal food restriction (FR) resulting in IUGR would decrease the overall immunotolerant milieu in the placenta, leading to increased cellular stress and death. Our specific objectives were to evaluate: (1) key cytokines (e.g. IL10) that regulate maternal-fetal tolerance, (2) cellular processes (autophagy and ER stress) that are immunologically-mediated and important for cellular survival and functioning, and (3) evaluate the resulting IUGR phenotype and placental histopathology. After subjecting pregnant mice to mild and moderate FR from gestational day (GD) 10 to 19, we collected placentas and embryos at GD19. We examined RNA sequencing data to identify immunologic pathways affected in IUGR-associated placentas and validated mRNA expression changes of genes important in cellular integrity. We also evaluated histopathologic changes in vascular and trophoblastic structures as well as protein expression changes in autophagy, ER stress, and apoptosis in the mouse placentas. Several differentially expressed genes were identified in FR compared to control mice, including a considerable subset that regulates immune tolerance, inflammation and cellular integrity. In summary, maternal food restriction decreases anti-inflammatory effect of IL10 and suppresses placental autophagic and ER stress responses, despite evidence of dysregulated vascular and trophoblast structures leading to IUGR.

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How to study placental vascular development?

Cited by 24 publications

References 54 publications

Mechanisms in Decorin Regulation of Vascular Endothelial Growth Factor-Induced Human Trophoblast Migration and Acquisition of Endothelial Phenotype1

Mechanisms in Decorin Regulation of Vascular Endothelial Growth Factor-Induced Human Trophoblast Migration and Acquisition of Endothelial Phenotype1

Human placenta-derived Wnt-5a induces the expression of ICAM-1 and VCAM-1 in CD133+CD34+-hematopoietic progenitor cells

Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction

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