Remodelling at the maternal–fetal interface: relevance to human pregnancy disorders

Cartwright, Judith E.; Fraser, Rupsha; Leslie, Karin; Wallace, Alison E.; James, Joanna L.

doi:10.1530/rep-10-0294

Cited by 238 publications

(170 citation statements)

References 87 publications

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“…Interestingly, IL10 is also reduced in women with PE (36). Uterine natural killer cells are the most abundant immune cell type at the maternal−fetal interface (27). IL11 significantly reduced placental IL15, required for uNK cell maturation and differentiation (37), and IL18, secreted by uNKs to mediate normal tissue remodeling (38).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Interleukin-11 alters placentation and causes preeclampsia features in mice

Winship

Koga

Menkhorst

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and proteinuria after 20 wk gestation. Abnormal extravillous trophoblast (EVT) invasion and remodeling of uterine spiral arterioles is thought to contribute to PE development. Interleukin-11 (IL11) impedes human EVT invasion in vitro and is elevated in PE decidua in women. We demonstrate that IL11 administered to mice causes development of PE features. Immunohistochemistry shows IL11 compromises trophoblast invasion, spiral artery remodeling, and placentation, leading to increased systolic blood pressure (SBP), proteinuria, and intrauterine growth restriction, although nonpregnant mice were unaffected. Real-time PCR array analysis identified pregnancy-associated plasma protein A2 (PAPPA2), associated with PE in women, as an IL11 regulated target. IL11 increased PAPPA2 serum and placental tissue levels in mice. In vitro, IL11 compromised primary human EVT invasion, whereas siRNA knockdown of PAPPA2 alleviated the effect. Genes regulating uterine natural killer (uNK) recruitment and differentiation were down-regulated and uNK cells were reduced after IL11 treatment in mice. IL11 withdrawal in mice at onset of PE features reduced SBP and proteinuria to control levels and alleviated placental labyrinth defects. In women, placental IL11 immunostaining levels increased in PE pregnancies and in serum collected from women before development of early-onset PE, shown by ELISA. These results indicate that elevated IL11 levels result in physiological changes at the maternal-fetal interface, contribute to abnormal placentation, and lead to the development of PE. Targeting placental IL11 may provide a new treatment option for PE.placenta | trophoblast | cytokines | pregnancy P reeclampsia (PE) is a pregnancy-induced disorder characterized by hypertension and proteinuria, unique to humans, affecting ∼8% of pregnancies (1). The etiology is poorly understood (2); nevertheless, there is substantial evidence showing abnormal placentation is the key underlying cause. During pregnancy, highly invasive extravillous trophoblasts (EVT) acquire vascular-like properties to remodel uterine spiral arterioles. This creates low-resistance, large-diameter vessels that promote uteroplacental blood supply to sustain fetal growth (3, 4). It is widely accepted that inadequate trophoblast invasion and impaired uterine spiral artery remodeling is an initiating factor in the development of PE (5). This is thought to impair uteroplacental arterial flow and lead to placental oxidative stress (6). PE is associated with increased placental secretion of proinflammatory cytokines (7) and angiogenic regulators (8), thought to contribute to widespread maternal endothelial dysfunction. The clinical symptoms of PE are hypertension, proteinuria, and peripheral and/or cerebral edema. Symptoms can differentially manifest during the second (early-onset, EO), or third (late-onset, LO) trimester (9). In addition to the maternal symptoms, PE is also frequently associated with prematurit...

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Section: Discussionmentioning

confidence: 99%

“…Immune cells function at the maternal−fetal interface to mediate maternal tolerance and facilitate decidual and arterial tissue remodeling during EVT invasion (27). IL11 reduced placental gene expression of IL10, IL15, and IL18 ( Fig.…”

Section: Il11 Alters Decidual Immune Cells Required For Normal Spiralmentioning

confidence: 99%

Interleukin-11 alters placentation and causes preeclampsia features in mice

Winship

Koga

Menkhorst

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…However, analysis techniques can influence results even when employed in the same dataset. In order to illustrate the importance of a judicious choice of analysis technique, here we consider both individual cell tracking and network analysis of a previously published time-lapse data set of the trophoblast cell line SGHPL-4 cultured alone or on top of a monolayer of human umbilical vein endothelial cells (HUVECs), 40 These cultures were then subjected to shear stress (with flow over the surface of the monolayer) of 0.5-6 dyne/cm 2 Here only results showing SGHPL-4 migrating in the absence of HUVECs and at 0.5 and 6 dyne/cm. 2 are shown, however results hold across experimental conditions.…”

Section: Quantifying Trophoblast Migrationmentioning

confidence: 99%

“…One such population-called extravillous trophoblasts (EVTs)-grow out from the placental villi and invade into the maternal decidua where they breach the maternal spiral arteries that supply blood to the placental surface and remodel these vessels into wide non-vasoactive structures. 1,2 For this process of spiral artery remodeling to be successful, 2 key trophoblast migration events are required 1) the migration of EVTs within the decidual stroma prior to arterial colonisation, and 2) the migration of a subset of EVTs (termed endovascular trophoblasts) along the arterial lumen down to the inner third of the myometrium. Trophoblast-induced remodeling of the spiral arteries results in an increased and constant supply of blood to the placenta as pregnancy progresses, and the importance of this process is highlighted in pregnancy disorders such as pre-eclampsia that are associated with inadequate spiral artery remodeling.…”

Section: Introductionmentioning

confidence: 99%

Quantifying trophoblast migration: In vitro approaches to address in vivo situations

James

Tun

Clark

2016

Cell Adhesion & Migration

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When trophoblasts migrate and invade in vivo, they do so by interacting with a range of other cell types, extracellular matrix proteins, chemotactic factors and physical forces such as fluid shear stress. These factors combine to influence overall trophoblast migration and invasion into the decidua, which in turn determines the success of spiral artery remodeling, and pregnancy itself. Our understanding of these important but complex processes is limited by the simplified conditions in which we often study cell migration in vitro, and many discrepancies are observed between different in vitro models in the literature. On top of these experimental considerations, the migration of individual trophoblasts can vary widely. While time-lapse microscopy provides a wealth of information on trophoblast migration, manual tracking of individual cell migration is a time consuming task that ultimately restricts the numbers of cells quantified, and thus the ability to extract meaningful information from the data. However, the development of automated imaging algorithms is likely to aid our ability to accurately interpret trophoblast migration in vitro, and better allow us to relate these observations to in vivo scenarios. This commentary discusses the advantages and disadvantages of techniques commonly used to quantify trophoblast migration and invasion, both from a cell biology and a mathematical perspective, and examines how such techniques could be improved to help us relate trophoblast migration more accurately to in vivo function in the future.

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“…A key event in endometrial decidualization, trophoblast implantation, and placentation is the degradation and remodeling of the extracellular matrix (ECM), which is determined by a careful balance between matrix synthesis, modification, and degradation [13]. Matrix-degrading enzymes include a large family of matrix metalloproteinases (MMPs), which comprises 23 endopeptidases in humans [14].…”

Section: Introductionmentioning

confidence: 99%

Functional single nucleotide polymorphisms of matrix metalloproteinase 7 and 12 genes in idiopathic recurrent spontaneous abortion

Barišić

Pereza

Hodžić

et al. 2016

J Assist Reprod Genet

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Purpose The aim of this study was to investigate the potential association of matrix metalloproteinase 7 (MMP7) -181 A/G and MMP12 -82 A/G functional single nucleotide polymorphisms (SNP) with idiopathic recurrent spontaneous abortion (IRSA) in Slovenian reproductive couples. Methods A case-control study was conducted on 149 couples with 3 or more consecutive idiopathic spontaneous pregnancy loses and 149 women and men with at least 2 live births and no history of pregnancy complications. Genotyping of MMP7 -181 A/G and MMP12 -82 A/G SNPs was performed using polymerase chain reaction and restriction fragment length polymorphism methods. Results There were no statistically significant differences in the distribution of MMP7 -181 A/G and MMP12 -82 A/G genotype, allele, or haplotype frequencies between IRSA patients and controls, as well as patients' primary and secondary IRSA. We also found no association of MMP7 -181 A/G and MMP12 -82 A/G genotypes, alleles, and haplotypes with IRSA. Conclusions We found no evidence to support the association between IRSA and MMP7 -181 A/G and MMP12 -82 A/G SNPs in Slovenian reproductive couples.

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Remodelling at the maternal–fetal interface: relevance to human pregnancy disorders

Cited by 238 publications

References 87 publications

Interleukin-11 alters placentation and causes preeclampsia features in mice

Interleukin-11 alters placentation and causes preeclampsia features in mice

Quantifying trophoblast migration: In vitro approaches to address in vivo situations

Functional single nucleotide polymorphisms of matrix metalloproteinase 7 and 12 genes in idiopathic recurrent spontaneous abortion

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