Molecular Cross-Talk at the Feto–Maternal Interface

Lash, Gendie E.

doi:10.1101/cshperspect.a023010

Cited by 52 publications

(44 citation statements)

References 166 publications

(181 reference statements)

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“…For example, the close contact between maternal and fetal tissues presents an immunological challenge to the mother, but immune tolerance is sustained throughout a healthy pregnancy. 22,23 Cross-talk between maternal and fetal tissues must therefore exist. 22 CMPs are candidates for communication between maternal and fetal sources as these pregnancy-associated microparticles have already been shown to carry immunomodulatory and regulatory proteins within the maternal circulation.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of proteomic biomarkers associated with circulating microparticles as an effective means to stratify the risk of spontaneous preterm birth

Cantonwine

Zhang

Rosenblatt

et al. 2016

American Journal of Obstetrics and Gynecology

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Background The analysis of circulating microparticles in pregnancy is of revolutionary potential as it represents an in vivo ‘biopsy’ of active gestational tissues. Objectives We hypothesize that circulating microparticle signaling will differ in pregnancies that experience spontaneous preterm birth from those delivering at term and that these differences will be evident many weeks in advance of clinical presentation. Study Design Utilizing plasma specimens obtained between 10–12 weeks gestation as part of a prospectively collected birth cohort where pregnancy outcomes are independently validated by two board certified Maternal Fetal Medicine physicians, 25 singleton cases of spontaneous preterm birth ≤34 weeks were matched by maternal age, race, and gestational age of sampling (+/− 2 weeks) to 50 uncomplicated term deliveries. Circulating microparticles s from these first trimester specimens were isolated and analyzed by multiple reaction monitoring mass spectrometry for potential protein biomarkers following from previous studies. Markers with robust univariate performance in correlating spontaneous preterm birth were further evaluated for their biological relevance via a combined functional profiling/pathway analysis, and for multivariate performance. Results Among the 132 proteins evaluated, 62 demonstrated robust power of detecting spontaneous preterm birth in bootstrap receiver-operating characteristic curve analysis at a false discovery rate of < 20% estimated via label permutation. Differential dependency network analysis identified spontaneous preterm birth -associated co-expression patterns linked to biological processes of inflammation, wound healing, and the coagulation cascade. Linear modeling of spontaneous preterm birth using a multiplex of the candidate biomarkers with a fixed sensitivity of 80% exhibited a specificity of 83% with median area under the curve of 0.89. These result indicate strong potential of multivariate model development for informative risk stratification. Conclusion This project has identified functional proteomic factors with associated biological processes that are already unique in their expression profiles at 10–12 weeks among women who go on to deliver spontaneously ≤34 weeks. These changes, with further validation, will allow the stratification of patients at risk of spontaneous preterm birth before clinical presentation.

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Section: Discussionmentioning

confidence: 99%

“…22,23 Cross-talk between maternal and fetal tissues must therefore exist. 22 CMPs are candidates for communication between maternal and fetal sources as these pregnancy-associated microparticles have already been shown to carry immunomodulatory and regulatory proteins within the maternal circulation. 24 …”

Section: Discussionmentioning

confidence: 99%

Evaluation of proteomic biomarkers associated with circulating microparticles as an effective means to stratify the risk of spontaneous preterm birth

Cantonwine

Zhang

Rosenblatt

et al. 2016

American Journal of Obstetrics and Gynecology

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“…The migratory and invasive properties of EVT are stringently controlled and derangement can lead to pathological conditions. Indeed, suboptimal trophoblast invasion has been associated with FGR and preeclampsia, whereas excessive trophoblast invasion has been linked to placenta accreta and choriocarcinoma (reviewed in [7, 8]).…”

Section: Introductionmentioning

confidence: 99%

H19 long noncoding RNA alters trophoblast cell migration and invasion by regulating TβR3 in placentae with fetal growth restriction

Zuckerwise

et al. 2016

Oncotarget

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Fetal growth restriction (FGR) is a well-recognized risk factor for perinatal mortality and morbidity, as well as neurodevelopmental impairment and adulthood onset disorders. Here we report that the H19 long noncoding RNA (lncRNA) is significantly decreased in placentae from pregnancies with FGR. Downregulation of H19 leads to reduced migration and invasion of extravillous trophoblast (EVT) cells in vitro. This is consistent with reduced trophoblast invasion that has been observed in FGR. Genome-scale transcriptome profiling of EVT cells reveals significantly decreased expression of the type III TGF-β receptor (TβR3) following H19 knockdown. Decreased TβR3 expression is also seen in FGR placentae. TβR3 repression decreases EVT cell migration and invasion, owing to impaired TGF-β signaling through a non-canonical TGF-β signaling pathway. Further, we identify TβR3 as a novel regulatory target of microRNA let-7. We propose that dysregulation of this newly identified H19/TβR3-mediated regulatory pathway may contribute to the molecular mechanism of FGR. Our findings are the first to show a lncRNA-based mechanism of FGR, holding promise for the development of novel predictive, diagnostic, and therapeutic modalities for FGR.

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“…Following trophoblast invasion, the placenta is anchored in the uterine wall, and extravillous trophoblasts of placenta further remodel the uterine spiral arteries to form low-resistance vessels, which is vital to ensure an adequate blood supply for optimal fetal growth [22, 24]. Excess invasion of trophoblast may result in chorionic epithelial carcinoma, whereas insufficient invasion of trophoblast may result in PE, early abortion, and intrauterine growth retardation [1, 15].…”

Section: Discussionmentioning

confidence: 99%

“…The invasion of placental trophoblast cells into the maternal decidua is a key process in the establishment of successful pregnancy [22, 23]. Following trophoblast invasion, the placenta is anchored in the uterine wall, and extravillous trophoblasts of placenta further remodel the uterine spiral arteries to form low-resistance vessels, which is vital to ensure an adequate blood supply for optimal fetal growth [22, 24].…”

Section: Discussionmentioning

confidence: 99%

Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels

Zhong

Chen

Ling

et al. 2018

Cell Physiol Biochem

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Background/Aims: Neuropathy target esterase (NTE, also known as neurotoxic esterase) is proven to deacylate phosphatidylcholine (PC) to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE)-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE. Methods: NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method. Results: NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels. Conclusions: Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway.

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Molecular Cross-Talk at the Feto–Maternal Interface

Cited by 52 publications

References 166 publications

Evaluation of proteomic biomarkers associated with circulating microparticles as an effective means to stratify the risk of spontaneous preterm birth

Evaluation of proteomic biomarkers associated with circulating microparticles as an effective means to stratify the risk of spontaneous preterm birth

H19 long noncoding RNA alters trophoblast cell migration and invasion by regulating TβR3 in placentae with fetal growth restriction

Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels

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