Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2

Virginia D Winn; Matthew Gormley; Agnes C Paquet; Kasper Kjær-Sørensen; Anita Kramer; Kristen K Rumer; Ronit Haimov-Kochman; Ru-Fang Yeh; Michael T Overgaard; Ajit Varki; Claus Oxvig; Susan J Fisher

doi:10.1210/en.2008-0990

Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2

Virginia D Winn, Matthew Gormley, Agnes C Paquet, Kasper Kjær-Sørensen, Anita Kramer, Kristen K Rumer, Ronit Haimov-Kochman, Ru-Fang Yeh, Michael T Overgaard, Ajit Varki, Claus Oxvig, Susan J Fisher

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

150 Citations (Scopus)

Abstract

Preeclampsia (PE), which affects 4-8% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. Within the basal plate, placental cytotrophoblasts (CTBs) of fetal origin invade the uterus and extensively remodel the maternal vasculature. In PE, CTB invasion is often shallow, and vascular remodeling is rudimentary. To better understand possible causes, we conducted a global analysis of gene expression at the maternal-fetal interface in placental samples from women with PE (n = 12; 24-36 wk) vs. samples from women who delivered due to preterm labor with no evidence of infection (n = 11; 24-36 wk), a condition that our previous work showed is associated with normal CTB invasion. Using the HG-U133A&B Affymetrix GeneChip platform, and statistical significance set at log odds-ratio of B >0, 55 genes were differentially expressed in PE. They encoded proteins previously associated with PE [e.g. Flt-1 (vascular endothelial growth factor receptor-1), leptin, CRH, and inhibin] and novel molecules [e.g. sialic acid binding Ig-like lectin 6 (Siglec-6), a potential leptin receptor, and pappalysin-2 (PAPP-A2), a protease that cleaves IGF-binding proteins]. We used quantitative PCR to validate the expression patterns of a subset of the genes. At the protein level, we confirmed PE-related changes in the expression of Siglec-6 and PAPP-A2, which localized to invasive CTBs and syncytiotrophoblasts. Notably, Siglec-6 placental expression is uniquely human, as is spontaneous PE. The functional significance of these novel observations may provide new insights into the pathogenesis of PE, and assaying the circulating levels of these proteins could have clinical utility for predicting and/or diagnosing PE.

Original language	English
Journal	Endocrinology
Volume	150
Issue	1
Pages (from-to)	452-62
Number of pages	10
ISSN	0013-7227
DOIs	https://doi.org/10.1210/en.2008-0990
Publication status	Published - 2008

Keywords

Antigens, CD
Antigens, Differentiation, Myelomonocytic
DNA Primers
Female
Gene Expression Regulation
Humans
Lectins
Maternal-Fetal Exchange
Oligonucleotide Array Sequence Analysis
Pre-Eclampsia
Pregnancy
Pregnancy-Associated Plasma Protein-A

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10.1210/en.2008-0990

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Winn, V. D., Gormley, M., Paquet, A. C., Kjær-Sørensen, K., Kramer, A., Rumer, K. K., Haimov-Kochman, R., Yeh, R.-F., Overgaard, M. T., Varki, A., Oxvig, C., & Fisher, S. J. (2008). Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2. Endocrinology, 150(1), 452-62. https://doi.org/10.1210/en.2008-0990

@article{d01d479022e111dfb95d000ea68e967b,

title = "Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2",

abstract = "Preeclampsia (PE), which affects 4-8% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. Within the basal plate, placental cytotrophoblasts (CTBs) of fetal origin invade the uterus and extensively remodel the maternal vasculature. In PE, CTB invasion is often shallow, and vascular remodeling is rudimentary. To better understand possible causes, we conducted a global analysis of gene expression at the maternal-fetal interface in placental samples from women with PE (n = 12; 24-36 wk) vs. samples from women who delivered due to preterm labor with no evidence of infection (n = 11; 24-36 wk), a condition that our previous work showed is associated with normal CTB invasion. Using the HG-U133A&B Affymetrix GeneChip platform, and statistical significance set at log odds-ratio of B >0, 55 genes were differentially expressed in PE. They encoded proteins previously associated with PE [e.g. Flt-1 (vascular endothelial growth factor receptor-1), leptin, CRH, and inhibin] and novel molecules [e.g. sialic acid binding Ig-like lectin 6 (Siglec-6), a potential leptin receptor, and pappalysin-2 (PAPP-A2), a protease that cleaves IGF-binding proteins]. We used quantitative PCR to validate the expression patterns of a subset of the genes. At the protein level, we confirmed PE-related changes in the expression of Siglec-6 and PAPP-A2, which localized to invasive CTBs and syncytiotrophoblasts. Notably, Siglec-6 placental expression is uniquely human, as is spontaneous PE. The functional significance of these novel observations may provide new insights into the pathogenesis of PE, and assaying the circulating levels of these proteins could have clinical utility for predicting and/or diagnosing PE.",

keywords = "Antigens, CD, Antigens, Differentiation, Myelomonocytic, DNA Primers, Female, Gene Expression Regulation, Humans, Lectins, Maternal-Fetal Exchange, Oligonucleotide Array Sequence Analysis, Pre-Eclampsia, Pregnancy, Pregnancy-Associated Plasma Protein-A",

author = "Winn, {Virginia D} and Matthew Gormley and Paquet, {Agnes C} and Kasper Kj{\ae}r-S{\o}rensen and Anita Kramer and Rumer, {Kristen K} and Ronit Haimov-Kochman and Ru-Fang Yeh and Overgaard, {Michael T} and Ajit Varki and Claus Oxvig and Fisher, {Susan J}",

year = "2008",

doi = "10.1210/en.2008-0990",

language = "English",

volume = "150",

pages = "452--62",

journal = "Endocrinology",

issn = "0013-7227",

publisher = "Endocrine Society",

number = "1",

}

Winn, VD, Gormley, M, Paquet, AC, Kjær-Sørensen, K, Kramer, A, Rumer, KK, Haimov-Kochman, R, Yeh, R-F, Overgaard, MT, Varki, A, Oxvig, C & Fisher, SJ 2008, 'Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2', Endocrinology, vol. 150, no. 1, pp. 452-62. https://doi.org/10.1210/en.2008-0990

Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2. / Winn, Virginia D; Gormley, Matthew; Paquet, Agnes C et al.
In: Endocrinology, Vol. 150, No. 1, 2008, p. 452-62.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2

AU - Winn, Virginia D

AU - Gormley, Matthew

AU - Paquet, Agnes C

AU - Kjær-Sørensen, Kasper

AU - Kramer, Anita

AU - Rumer, Kristen K

AU - Haimov-Kochman, Ronit

AU - Yeh, Ru-Fang

AU - Overgaard, Michael T

AU - Varki, Ajit

AU - Oxvig, Claus

AU - Fisher, Susan J

PY - 2008

Y1 - 2008

N2 - Preeclampsia (PE), which affects 4-8% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. Within the basal plate, placental cytotrophoblasts (CTBs) of fetal origin invade the uterus and extensively remodel the maternal vasculature. In PE, CTB invasion is often shallow, and vascular remodeling is rudimentary. To better understand possible causes, we conducted a global analysis of gene expression at the maternal-fetal interface in placental samples from women with PE (n = 12; 24-36 wk) vs. samples from women who delivered due to preterm labor with no evidence of infection (n = 11; 24-36 wk), a condition that our previous work showed is associated with normal CTB invasion. Using the HG-U133A&B Affymetrix GeneChip platform, and statistical significance set at log odds-ratio of B >0, 55 genes were differentially expressed in PE. They encoded proteins previously associated with PE [e.g. Flt-1 (vascular endothelial growth factor receptor-1), leptin, CRH, and inhibin] and novel molecules [e.g. sialic acid binding Ig-like lectin 6 (Siglec-6), a potential leptin receptor, and pappalysin-2 (PAPP-A2), a protease that cleaves IGF-binding proteins]. We used quantitative PCR to validate the expression patterns of a subset of the genes. At the protein level, we confirmed PE-related changes in the expression of Siglec-6 and PAPP-A2, which localized to invasive CTBs and syncytiotrophoblasts. Notably, Siglec-6 placental expression is uniquely human, as is spontaneous PE. The functional significance of these novel observations may provide new insights into the pathogenesis of PE, and assaying the circulating levels of these proteins could have clinical utility for predicting and/or diagnosing PE.

AB - Preeclampsia (PE), which affects 4-8% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. Within the basal plate, placental cytotrophoblasts (CTBs) of fetal origin invade the uterus and extensively remodel the maternal vasculature. In PE, CTB invasion is often shallow, and vascular remodeling is rudimentary. To better understand possible causes, we conducted a global analysis of gene expression at the maternal-fetal interface in placental samples from women with PE (n = 12; 24-36 wk) vs. samples from women who delivered due to preterm labor with no evidence of infection (n = 11; 24-36 wk), a condition that our previous work showed is associated with normal CTB invasion. Using the HG-U133A&B Affymetrix GeneChip platform, and statistical significance set at log odds-ratio of B >0, 55 genes were differentially expressed in PE. They encoded proteins previously associated with PE [e.g. Flt-1 (vascular endothelial growth factor receptor-1), leptin, CRH, and inhibin] and novel molecules [e.g. sialic acid binding Ig-like lectin 6 (Siglec-6), a potential leptin receptor, and pappalysin-2 (PAPP-A2), a protease that cleaves IGF-binding proteins]. We used quantitative PCR to validate the expression patterns of a subset of the genes. At the protein level, we confirmed PE-related changes in the expression of Siglec-6 and PAPP-A2, which localized to invasive CTBs and syncytiotrophoblasts. Notably, Siglec-6 placental expression is uniquely human, as is spontaneous PE. The functional significance of these novel observations may provide new insights into the pathogenesis of PE, and assaying the circulating levels of these proteins could have clinical utility for predicting and/or diagnosing PE.

KW - Antigens, CD

KW - Antigens, Differentiation, Myelomonocytic

KW - DNA Primers

KW - Female

KW - Gene Expression Regulation

KW - Humans

KW - Lectins

KW - Maternal-Fetal Exchange

KW - Oligonucleotide Array Sequence Analysis

KW - Pre-Eclampsia

KW - Pregnancy

KW - Pregnancy-Associated Plasma Protein-A

U2 - 10.1210/en.2008-0990

DO - 10.1210/en.2008-0990

M3 - Journal article

C2 - 18818296

SN - 0013-7227

VL - 150

SP - 452

EP - 462

JO - Endocrinology

JF - Endocrinology

IS - 1

ER -

Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2

Abstract

Keywords

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