Siglec-6 Expression Is Increased in Placentas From Pregnancies Complicated by Preterm Preeclampsia

Rumer, Kristen K.; Uyenishi, Jill; Hoffman, M. Camille; Fisher, Barbra M.; Winn, Virginia D.

doi:10.1177/1933719112461185

Cited by 37 publications

(25 citation statements)

References 26 publications

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“…A recent report has documented an increase in Siglec-6 expression in the placenta following spontaneous labor and delivery in comparison to those following elective cesarean section without labor; therefore, it has been proposed that this molecule may play a role in the process of parturition (270,271). In addition, increased Siglec-6 trophoblast expression was reported in women with gestational trophoblastic disease and those with preterm preeclampsia (124, 269,[272][273][274]. The findings in Siglec-6 reported herein provide further support that an increase in abundance of this protein, detected with current technology in the maternal circulation, may have biological and clinical implications.…”

Section: Meaning Of the Studysupporting

confidence: 75%

The maternal plasma proteome changes as a function of gestational age in normal pregnancy: a longitudinal study

Romero

Erez

Maymon

et al. 2017

American Journal of Obstetrics and Gynecology

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Objective Pregnancy is accompanied by dramatic physiologic changes in maternal plasma proteins. Characterization of the maternal plasma proteome in normal pregnancy is an essential step for understanding changes to predict pregnancy outcome. The objective of this study was to describe maternal plasma proteins that change in abundance with advancing gestational age, and determine biological processes that are perturbed in normal pregnancy. Materials and methods A longitudinal study included 43 normal pregnancies that had a term delivery of an infant who was appropriate for gestational age (AGA) without maternal or neonatal complications. For each pregnancy, 3 to 6 maternal plasma samples (median=5,) were profiled to measure the abundance of 1,125 proteins using multiplex assays. Linear mixed effects models with polynomial splines were used to model protein abundance as a function of gestational age, and significance of the association was inferred via likelihood ratio tests. Proteins considered to be significantly changed were defined as having: 1) more than 1.5 fold change between 8 and 40 weeks of gestation; and 2) a false discovery rate (FDR) adjusted p-value <0.1. Gene ontology enrichment analysis was employed to identify biological processes over-represented among the proteins that changed with advancing gestation. Results 1) Ten percent (112/1,125) of the profiled proteins changed in abundance as a function of gestational age; 2) of the 1,125 proteins analyzed Glypican-3, sialic acid-binding immunoglobulin-type lectins (Siglec)-6, placental growth factor (PlGF), C-C motif (CCL)-28, carbonic anhydrase 6, Prolactin (PRL), interleukin-1 receptor 4 (IL-1 R4), dual specificity mitogen-activated protein kinase 4 (MP2K4) and pregnancy-associated plasma protein-A (PAPP-A) had more than 5 fold change in abundance across gestation. These 9 proteins are known to be involved in a wide range of both physiologic and pathologic processes, such as growth regulation, embryogenesis, angiogenesis immunoregulation, inflammation etc.; and 3) biological processes associated with protein changes in normal pregnancy included defense response, defense response to bacteria, proteolysis and leukocyte migration (FDR=10%). Conclusions The plasma proteome of normal pregnancy demonstrates dramatic changes in both magnitude of changes and the fraction of the proteins involved. Such information is important to understand the physiology of pregnancy, development of biomarkers to differentiate normal vs. abnormal pregnancy, and determine the response to interventions.

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Section: Meaning Of the Studysupporting

confidence: 75%

The maternal plasma proteome changes as a function of gestational age in normal pregnancy: a longitudinal study

Romero

Erez

Maymon

et al. 2017

American Journal of Obstetrics and Gynecology

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“…Members of this cluster are used as biomarkers and have been shown to play a functional role in pre-eclampsia [46]–[48]. Also the clusters around INH(B)A, CGA/CGB, and LEP have previously been reported to be affected in the pre-eclamptic placenta and some cluster members have been evaluated in the circulation of affected women [49]–[56].…”

Section: Discussionmentioning

confidence: 99%

Differentially Expressed Genes in the Pre-Eclamptic Placenta: A Systematic Review and Meta-Analysis

et al. 2013

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ObjectiveTo systematically review the literature on human gene expression data of placental tissue in pre-eclampsia and to characterize a meta-signature of differentially expressed genes in order to identify novel putative diagnostic markers.Data SourcesMedline through 11 February 2011 using MeSH terms and keywords related to placenta, gene expression and gene expression arrays; GEO database using the term “placent*”; and reference lists of eligible primary studies, without constraints.MethodsFrom 1068 studies retrieved from the search, we included original publications that had performed gene expression array analyses of placental tissue in the third trimester and that reported on differentially expressed genes in pre-eclampsia versus normotensive controls. Two reviewers independently identified eligible studies, extracted descriptive and gene expression data and assessed study quality. Using a vote-counting method based on a comparative meta-profiling algorithm, we determined a meta-signature that characterizes the significant intersection of differentially expressed genes from the collection of independent gene signatures.ResultsWe identified 33 eligible gene expression array studies of placental tissue in the 3rd trimester comprising 30 datasets on mRNA expression and 4 datasets on microRNA expression. The pre-eclamptic placental meta-signature consisted of 40 annotated gene transcripts and 17 microRNAs. At least half of the mRNA transcripts encode a protein that is secreted from the cell and could potentially serve as a biomarker.ConclusionsIn addition to well-known and validated genes, we identified 14 transcripts not reported previously in relation to pre-eclampsia of which the majority is also expressed in the 1st trimester placenta, and three encode a secreted protein.

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“…An attribute only defining the human placenta is the expression of sialic acid-binding Ig-like lectin-6 (siglec-6) on trophoblast cells, probably due to human-specific changes in the promoter sequences (Brinkman- Van der Linden et al, 2007). Siglec-6 is upregulated in placentas from women with preeclampsia (Winn et al, 2009, Rumer et al, 2013. Indeed, Lam et al (2011) discovered that the uterine isoform glycodelin A interacts with siglec-6, thus lowering the invasive potential of trophoblast cells (Lam et al, 2011).…”

Section: Siglec-6 Imup-2 and Galectinsmentioning

confidence: 96%

Only humans have human placentas: molecular differences between mice and humans

Schmidt¹,

Morales-Prieto²,

Pastuschek³

et al. 2015

Journal of Reproductive Immunology

175

117

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Siglec-6 Expression Is Increased in Placentas From Pregnancies Complicated by Preterm Preeclampsia

Cited by 37 publications

References 26 publications

The maternal plasma proteome changes as a function of gestational age in normal pregnancy: a longitudinal study

The maternal plasma proteome changes as a function of gestational age in normal pregnancy: a longitudinal study

Differentially Expressed Genes in the Pre-Eclamptic Placenta: A Systematic Review and Meta-Analysis

Only humans have human placentas: molecular differences between mice and humans

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