Differential expression of human placental PAPP-A2 over gestation and in preeclampsia

Kramer, Anita; Lamale‐Smith, Leah; Winn, Virginia D.

doi:10.1016/j.placenta.2015.11.004

Cited by 38 publications

(28 citation statements)

References 29 publications

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“…PAPP-A2 acts in the regulation of growth factors during trophoblast invasion. The levels were elevated in maternal sera and placental tissue during PE [119].…”

Section: Prediction and Putative Biomarkersmentioning

confidence: 95%

Immunology of hepatic diseases during pregnancy

2016

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The mother's immune system has to adapt to pregnancy accepting the semi-allograft fetus and preventing harmful effects to the developing child. Aberrations in feto-maternal immune adaptation may result in disease of the mother, such as liver injury. Five pregnancy-associated liver disorders have been described so far, however, little is known concerning immune alterations promoting the respective disease. These liver disorders are pre-eclampsia, hemolysis, elevated liver enzymes, low platelet count (HELLP), acute fatty liver, hyperemesis gravidarum, and intrahepatic cholestasis of pregnancy. On the other hand, pre-existing autoimmune liver injury of the mother can be affected by pregnancy. This review intends to summarize current knowledge linking feto-maternal immunology and liver inflammation with a special emphasis on novel potential biomarkers.

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“…PAPP-A2 acts in the regulation of growth factors during trophoblast invasion. The levels were elevated in maternal sera and placental tissue during PE [119].…”

Section: Prediction and Putative Biomarkersmentioning

confidence: 95%

Immunology of hepatic diseases during pregnancy

2016

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“…Among these genes, PAPPA-2 is the gene with the largest number of methylation sites significantly altered (hypomethylation), and with the largest number of transcripts significantly differently expressed (overexpression) in IUGR placentas. Its overexpression has already been reported in both maternal blood and the placenta in IUGR (Whitehead et al, 2013) and PE (Kramer et al, 2016). PAPPA-2 encodes a protein cleaving the insulin-like growth factor 1 (IGF-1) from a ternary complex with IGF binding proteins (IGFBP-3) (Fujimoto et al, 2017).…”

Section: Energy Metabolism and Insulin Resistancementioning

confidence: 99%

Data-Mining Approach on Transcriptomics and Methylomics Placental Analysis Highlights Genes in Fetal Growth Restriction

et al. 2020

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Intrauterine Growth Restriction (IUGR) affects 8% of newborns and increases morbidity and mortality for the offspring even during later stages of life. Single omics studies have evidenced epigenetic, genetic, and metabolic alterations in IUGR, but pathogenic mechanisms as a whole are not being fully understood. An in-depth strategy combining methylomics and transcriptomics analyses was performed on 36 placenta samples in a case-control study. Data-mining algorithms were used to combine the analysis of more than 1,200 genes found to be significantly expressed and/or methylated. We used an automated text-mining approach, using the bulk textual gene annotations of the discriminant genes. Machine learning models were then used to explore the phenotypic subgroups (premature birth, birth weight, and head circumference) associated with IUGR. Gene annotation clustering highlighted the alteration of cell signaling and proliferation, cytoskeleton and cellular structures, oxidative stress, protein turnover, muscle development, energy, and lipid metabolism with insulin resistance. Machine learning models showed a high capacity for predicting the sub-phenotypes associated with IUGR, allowing a better description of the IUGR pathophysiology as well as key genes involved.

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“…STC1 was reported to inhibit the proteolytic activity of PAPP-A and PAPP-A2 in vitro (12). Reduced maternal serum PAPP-A levels refer to a high PE risk (21), whereas maternal sera and placental tissues from PE cases show, in contrast, elevated levels of PAPP-A2 (22). We speculate that increased circulating STC1 in PE pregnancy may represent a feedback mechanism to high expression of PAPP-A2.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a recent study demonstrated that STC1 is a proteinase inhibitor of the pregnancy-associated plasma protein (PAPP)-A and PAPP-A2, modulating IGF signaling (12). Both encoding genes, PAPPA and PAPPA2 , are among the most highly expressed genes in the human placenta (20), and their altered expression has been linked to PE (21, 22). …”

mentioning

confidence: 99%

Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators

Juhanson

Rull

Kikas

et al. 2016

The Journal of Clinical Endocrinology & Metabolism

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Context and Objectives:The study represents the first comprehensive analysis of Stanniocalcin-1 (STC1) hormone in human pregnancy, assessing clinical, lifestyle, and genetic determinants of circulating STC1 at term.Design, Setting, and Participants:Participants included women with (n = 50) and without (n = 316) preeclampsia (PE) at delivery, recruited in the REPROgrammed fetal and/or maternal METAbolism (REPROMETA) study (2006–2011, Estonia). Genetic association analysis combined PE cases (n = 597) and controls (n = 623) from the REPROMETA and Finnish Genetics of Preeclampsia Consortium (2008–2011) studies.Main Outcome Measure(s):Maternal postpartum plasma STC1 was measured by ELISA (n = 366) and placental STC1 gene expression by TaqMan quantitative RT-PCR (n = 120). Genotyping was performed using Sequenom MassArray.Results:Significantly higher STC1 plasma level was measured for the PE (median, 1952 pg/mL; 1030–4284 pg/mL) compared with non-PE group (median, 1562 pg/mL; 423–3781 pg/mL; P = 3.7 × 10−4, Mann-Whitney U test). Statistical significance was enhanced after adjustment for cofactors (linear regression, P = 1.8 × 10−6). STC1 measurements were negatively correlated with maternal smoking. Prepregnancy body mass index had a positive correlation with STC1 only among PE patients (r = 0.45; P = .001). The strongest genetic association with hormone concentrations was detected for STC1 single nucleotide polymorphisms rs3758089 (C allele: minor allele frequency, 5%; linear regression: β = 249.2 pg/mL; P = .014) and rs12678447 (G allele: minor allele frequency, 7%; β = 147.0 pg/mL; P = .082). rs12678447 placental genotypes were significantly associated with STC1 gene expression (P = .014). The REPROMETA/Finnish Genetics of Preeclampsia Consortium meta-analysis suggested an increased risk to develop late-onset PE for the rs12678447 G allele carriers (P = .05; odds ratio = 1.38 [0.98–1.93]).Conclusions:Increased STC1 hormone represents a hallmark of late-onset PE. STC1 gene variants modulate placental gene expression and maternal hormone levels.

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Differential expression of human placental PAPP-A2 over gestation and in preeclampsia

Cited by 38 publications

References 29 publications

Immunology of hepatic diseases during pregnancy

Immunology of hepatic diseases during pregnancy

Data-Mining Approach on Transcriptomics and Methylomics Placental Analysis Highlights Genes in Fetal Growth Restriction

Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators

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