Placental Biglycan Expression is Decreased in Human Idiopathic Fetal Growth Restriction

Abstract Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. The majority of FGR cases are idiopathic and are associated with placental insufficiency, which can result from placental thrombosis. Evidence suggests that Dermatan Sulfate (DS) is an important anti-coa...

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Veröffentlicht in:Placenta (Eastbourne) 2010-08, Vol.31 (8), p.712-717
Hauptverfasser: Murthi, P, Faisal, F.A, Rajaraman, G, Stevenson, J, Ignjatovic, V, Monagle, P.T, Brennecke, S.P, Said, J.M
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container_end_page 717
container_issue 8
container_start_page 712
container_title Placenta (Eastbourne)
container_volume 31
creator Murthi, P
Faisal, F.A
Rajaraman, G
Stevenson, J
Ignjatovic, V
Monagle, P.T
Brennecke, S.P
Said, J.M
description Abstract Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. The majority of FGR cases are idiopathic and are associated with placental insufficiency, which can result from placental thrombosis. Evidence suggests that Dermatan Sulfate (DS) is an important anti-coagulant in placentae of uncomplicated pregnancies. This study hypothesised that the expression of biglycan proteoglycan, a source of DS, is decreased in idiopathic FGR placentae compared with placentae from uncomplicated pregnancies. This study aimed to determine biglycan mRNA, protein expression and spatial distribution in idiopathic FGR placentae compared with the placentae from gestation-matched controls. Biglycan mRNA expression, protein expression and spatial distribution was determined in 26 idiopathic FGR-affected placentae and 27 placentae from gestation-matched controls (27–40 weeks gestation) using real-time PCR, immunoblotting and immunohistochemistry, respectively. Mean biglycan mRNA expression was significantly decreased in FGR placentae compared with control placentae (2.87 ± 0.55, ( n  = 26) vs. 4.48 ± 0.85, ( n  = 27); t -test p  = 0.01). FGR placentae demonstrated a trend towards decrease in mean biglycan protein expression compared with control placentae (0.86 ± 0.22 ( n  = 9, FGR) vs, 1.9 ± 0.56 ( n  = 7, control) p  = 0.07). Biglycan immunoreactivity was detected in endothelial cells and sub-endothelial cells of the perivascular region of fetal capillaries. Semi-quantitative analyses demonstrated a significant decrease in immunoreactive biglycan in FGR placentae compared with control placentae (51.1 ± 19.3 vs, 500.7 ± 223, n  = 6, p  
doi_str_mv 10.1016/j.placenta.2010.05.009
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The majority of FGR cases are idiopathic and are associated with placental insufficiency, which can result from placental thrombosis. Evidence suggests that Dermatan Sulfate (DS) is an important anti-coagulant in placentae of uncomplicated pregnancies. This study hypothesised that the expression of biglycan proteoglycan, a source of DS, is decreased in idiopathic FGR placentae compared with placentae from uncomplicated pregnancies. This study aimed to determine biglycan mRNA, protein expression and spatial distribution in idiopathic FGR placentae compared with the placentae from gestation-matched controls. Biglycan mRNA expression, protein expression and spatial distribution was determined in 26 idiopathic FGR-affected placentae and 27 placentae from gestation-matched controls (27–40 weeks gestation) using real-time PCR, immunoblotting and immunohistochemistry, respectively. Mean biglycan mRNA expression was significantly decreased in FGR placentae compared with control placentae (2.87 ± 0.55, ( n  = 26) vs. 4.48 ± 0.85, ( n  = 27); t -test p  = 0.01). FGR placentae demonstrated a trend towards decrease in mean biglycan protein expression compared with control placentae (0.86 ± 0.22 ( n  = 9, FGR) vs, 1.9 ± 0.56 ( n  = 7, control) p  = 0.07). Biglycan immunoreactivity was detected in endothelial cells and sub-endothelial cells of the perivascular region of fetal capillaries. Semi-quantitative analyses demonstrated a significant decrease in immunoreactive biglycan in FGR placentae compared with control placentae (51.1 ± 19.3 vs, 500.7 ± 223, n  = 6, p  &lt; 0.001). This is the first study to demonstrate decreased biglycan expression in idiopathic FGR placentae compared to gestation-matched controls. 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Mean biglycan mRNA expression was significantly decreased in FGR placentae compared with control placentae (2.87 ± 0.55, ( n  = 26) vs. 4.48 ± 0.85, ( n  = 27); t -test p  = 0.01). FGR placentae demonstrated a trend towards decrease in mean biglycan protein expression compared with control placentae (0.86 ± 0.22 ( n  = 9, FGR) vs, 1.9 ± 0.56 ( n  = 7, control) p  = 0.07). Biglycan immunoreactivity was detected in endothelial cells and sub-endothelial cells of the perivascular region of fetal capillaries. Semi-quantitative analyses demonstrated a significant decrease in immunoreactive biglycan in FGR placentae compared with control placentae (51.1 ± 19.3 vs, 500.7 ± 223, n  = 6, p  &lt; 0.001). This is the first study to demonstrate decreased biglycan expression in idiopathic FGR placentae compared to gestation-matched controls. Reduced biglycan expression may contribute to placental thrombosis within the fetal vasculature, and may contribute to the pathogenesis of idiopathic FGR.</description><subject>Adult</subject><subject>Biglycan - metabolism</subject><subject>Case-Control Studies</subject><subject>Dermatan sulphate</subject><subject>Female</subject><subject>Fetal growth restriction</subject><subject>Fetal Growth Retardation - metabolism</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Infant, Newborn</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Obstetrics and Gynecology</subject><subject>Placenta</subject><subject>Placenta - metabolism</subject><subject>Pregnancy</subject><subject>Proteoglycans</subject><subject>RNA, Messenger - metabolism</subject><issn>0143-4004</issn><issn>1532-3102</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAUxK2qqF1avkKVG6cs7zm2E18QtPSfVAlEQRwtr_NCvWST1E6A_fY42i2HXnqyZP1mxp5h7AxhiYDq3Xo5tNZRN9olh3QJcgmgD9gCZcHzAoEfsgWgKHIBII7Z6xjXkAiB_Igdc5AaRVkt2I8ve5s2O_c_262zXXb5dwgUo--7zMfsE7lANlKd-S67mTYJuK19P9jxwbvsimbpdej_jA_ZV4pj8G5MylP2qrFtpDf784R9v7r8dnGT332-vr34eJc7wfmYc0WIugYJjbYKlIKyUco5KgmpEFVdSdSy0YWUKycrjlWpSXFpNQhcNVCcsLc73yH0j1PKNxsfHbWt7aifoilFpaVSQidS7UgX-hgDNWYIfmPD1iCYuVOzNk-dmrlTA9KkxpLwbB8xrTZU_5c9lZiADzuA0kd_ewomOk-do9oHcqOpe_9yxvtnFq71nXe2_UVbiut-Cl2q0aCJ3IC5n5edh8W0aXqHLP4BXUWfMQ</recordid><startdate>20100801</startdate><enddate>20100801</enddate><creator>Murthi, P</creator><creator>Faisal, F.A</creator><creator>Rajaraman, G</creator><creator>Stevenson, J</creator><creator>Ignjatovic, V</creator><creator>Monagle, P.T</creator><creator>Brennecke, S.P</creator><creator>Said, J.M</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20100801</creationdate><title>Placental Biglycan Expression is Decreased in Human Idiopathic Fetal Growth Restriction</title><author>Murthi, P ; Faisal, F.A ; Rajaraman, G ; Stevenson, J ; Ignjatovic, V ; Monagle, P.T ; Brennecke, S.P ; Said, J.M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-26e119d050f9a606607f66cce7e1e348d85195f9355bc5821879e625a9041bf03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Biglycan - metabolism</topic><topic>Case-Control Studies</topic><topic>Dermatan sulphate</topic><topic>Female</topic><topic>Fetal growth restriction</topic><topic>Fetal Growth Retardation - metabolism</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Infant, Newborn</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Obstetrics and Gynecology</topic><topic>Placenta</topic><topic>Placenta - metabolism</topic><topic>Pregnancy</topic><topic>Proteoglycans</topic><topic>RNA, Messenger - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Murthi, P</creatorcontrib><creatorcontrib>Faisal, F.A</creatorcontrib><creatorcontrib>Rajaraman, G</creatorcontrib><creatorcontrib>Stevenson, J</creatorcontrib><creatorcontrib>Ignjatovic, V</creatorcontrib><creatorcontrib>Monagle, P.T</creatorcontrib><creatorcontrib>Brennecke, S.P</creatorcontrib><creatorcontrib>Said, J.M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Placenta (Eastbourne)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Murthi, P</au><au>Faisal, F.A</au><au>Rajaraman, G</au><au>Stevenson, J</au><au>Ignjatovic, V</au><au>Monagle, P.T</au><au>Brennecke, S.P</au><au>Said, J.M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Placental Biglycan Expression is Decreased in Human Idiopathic Fetal Growth Restriction</atitle><jtitle>Placenta (Eastbourne)</jtitle><addtitle>Placenta</addtitle><date>2010-08-01</date><risdate>2010</risdate><volume>31</volume><issue>8</issue><spage>712</spage><epage>717</epage><pages>712-717</pages><issn>0143-4004</issn><eissn>1532-3102</eissn><abstract>Abstract Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. The majority of FGR cases are idiopathic and are associated with placental insufficiency, which can result from placental thrombosis. Evidence suggests that Dermatan Sulfate (DS) is an important anti-coagulant in placentae of uncomplicated pregnancies. This study hypothesised that the expression of biglycan proteoglycan, a source of DS, is decreased in idiopathic FGR placentae compared with placentae from uncomplicated pregnancies. This study aimed to determine biglycan mRNA, protein expression and spatial distribution in idiopathic FGR placentae compared with the placentae from gestation-matched controls. Biglycan mRNA expression, protein expression and spatial distribution was determined in 26 idiopathic FGR-affected placentae and 27 placentae from gestation-matched controls (27–40 weeks gestation) using real-time PCR, immunoblotting and immunohistochemistry, respectively. Mean biglycan mRNA expression was significantly decreased in FGR placentae compared with control placentae (2.87 ± 0.55, ( n  = 26) vs. 4.48 ± 0.85, ( n  = 27); t -test p  = 0.01). FGR placentae demonstrated a trend towards decrease in mean biglycan protein expression compared with control placentae (0.86 ± 0.22 ( n  = 9, FGR) vs, 1.9 ± 0.56 ( n  = 7, control) p  = 0.07). Biglycan immunoreactivity was detected in endothelial cells and sub-endothelial cells of the perivascular region of fetal capillaries. Semi-quantitative analyses demonstrated a significant decrease in immunoreactive biglycan in FGR placentae compared with control placentae (51.1 ± 19.3 vs, 500.7 ± 223, n  = 6, p  &lt; 0.001). This is the first study to demonstrate decreased biglycan expression in idiopathic FGR placentae compared to gestation-matched controls. Reduced biglycan expression may contribute to placental thrombosis within the fetal vasculature, and may contribute to the pathogenesis of idiopathic FGR.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>20591478</pmid><doi>10.1016/j.placenta.2010.05.009</doi><tpages>6</tpages></addata></record>
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subjects Adult
Biglycan - metabolism
Case-Control Studies
Dermatan sulphate
Female
Fetal growth restriction
Fetal Growth Retardation - metabolism
Gene expression
Humans
Infant, Newborn
Internal Medicine
Male
Obstetrics and Gynecology
Placenta
Placenta - metabolism
Pregnancy
Proteoglycans
RNA, Messenger - metabolism
title Placental Biglycan Expression is Decreased in Human Idiopathic Fetal Growth Restriction
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