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GDM Alters Expression of Placental Estrogen Receptor α in a Cell Type and Gender-Specific Manner
Objective: The nuclear receptor estrogen receptor α (ERα) is one of the key players in energy balance, insulin resistance, and trophoblast differentiation. We tested the hypothesis that gestational diabetes mellitus (GDM) alters expression of placental ERα in a cell type-specific manner and that thi...
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| Published in: | Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2015-12, Vol.22 (12), p.1488-1495 |
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| Main Authors: | , , , , , , , , , |
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| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c3367-9a70110ffda640af99a47250cea37ea12234e4ec70463081a8944ee4741bd5cb3 |
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| cites | cdi_FETCH-LOGICAL-c3367-9a70110ffda640af99a47250cea37ea12234e4ec70463081a8944ee4741bd5cb3 |
| container_end_page | 1495 |
| container_issue | 12 |
| container_start_page | 1488 |
| container_title | Reproductive sciences (Thousand Oaks, Calif.) |
| container_volume | 22 |
| creator | Knabl, Julia Hiden, Ursula Hüttenbrenner, Rebecca Riedel, Christina Hutter, Stefan Kirn, Verena Günthner-Biller, Margit Desoye, Gernot Kainer, Franz Jeschke, Udo |
| description | Objective:
The nuclear receptor estrogen receptor α (ERα) is one of the key players in energy balance, insulin resistance, and trophoblast differentiation. We tested the hypothesis that gestational diabetes mellitus (GDM) alters expression of placental ERα in a cell type-specific manner and that this regulation may involve epigenetic changes.
Study Design:
Expression of ERα was analyzed by immunohistochemistry using the semiquantitative immunoreactive score in 80 placentas (40 GDM/40 controls). Quantitative real-time polymerase chain reaction (PCR) measured ERα messenger RNA (mRNA) in decidual tissue. Methylation-specific PCR was performed to analyze cytosine-phosphatidyl-guanine-island methylation of the ERα promoter.
Results:
Expression of ERα protein is upregulated (P = .011) in GDM in extravillous trophoblasts but not in syncytiotrophoblast. Gestational diabetes mellitus downregulated ERα in decidual vessels only in pregnancies with male but not female fetuses. Furthermore, mRNA of the ERα encoding gene estrogen receptor gene 1 (ESR1) was increased (+1.77 fold) in GDM decidua when compared to controls (P = .024). In parallel, the promoter of ESR1 was methylated only in decidua of healthy control individuals but not in GDM.
Conclusion:
Gestational diabetes mellitus affects expression of placental ERα in a cell type-dependent way, on epigenetic level. These data link GDM with epigenetic deregulations of ERα expression and open new insights into the intrauterine programming hypothesis of GDM. |
| doi_str_mv | 10.1177/1933719115585147 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1733189612</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_1933719115585147</sage_id><sourcerecordid>1733189612</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3367-9a70110ffda640af99a47250cea37ea12234e4ec70463081a8944ee4741bd5cb3</originalsourceid><addsrcrecordid>eNqNkM9OwzAMxiMEYuPPnRPKkUshbtKlOU5jDCQQCMa58lJ36tSlJekk9li8CM9E0TYOHBAnW_bv-2R_jJ2BuATQ-gqMlBoMQJKkCSi9x_rfo0jHItnf9d2-x45CWAiRKBOnh6wXJ0bp1MR9hpPrBz6sWvKBj98bTyGUteN1wZ8qtORarPg4tL6ek-PPZKlpa88_P3jpOPIRVRWfrhvi6HI-IZeTj14asmVRWv6AzpE_YQcFVoFOt_WYvd6Mp6Pb6P5xcjca3kdWyoGODGoBIIoix4ESWBiDSseJsIRSE0IcS0WKrBZqIEUKmBqliJRWMMsTO5PH7GLj2_j6bUWhzZZlsN2B6KhehQy0lJCaAcQdKjao9XUInoqs8eUS_ToDkX0Hm_0OtpOcb91XsyXlP4Jdkh0AGyB0Kzcnny3qlXfdx3-ZRlsNzukf_Bf7Ho3R</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1733189612</pqid></control><display><type>article</type><title>GDM Alters Expression of Placental Estrogen Receptor α in a Cell Type and Gender-Specific Manner</title><source>Springer Nature</source><creator>Knabl, Julia ; Hiden, Ursula ; Hüttenbrenner, Rebecca ; Riedel, Christina ; Hutter, Stefan ; Kirn, Verena ; Günthner-Biller, Margit ; Desoye, Gernot ; Kainer, Franz ; Jeschke, Udo</creator><creatorcontrib>Knabl, Julia ; Hiden, Ursula ; Hüttenbrenner, Rebecca ; Riedel, Christina ; Hutter, Stefan ; Kirn, Verena ; Günthner-Biller, Margit ; Desoye, Gernot ; Kainer, Franz ; Jeschke, Udo</creatorcontrib><description>Objective:
The nuclear receptor estrogen receptor α (ERα) is one of the key players in energy balance, insulin resistance, and trophoblast differentiation. We tested the hypothesis that gestational diabetes mellitus (GDM) alters expression of placental ERα in a cell type-specific manner and that this regulation may involve epigenetic changes.
Study Design:
Expression of ERα was analyzed by immunohistochemistry using the semiquantitative immunoreactive score in 80 placentas (40 GDM/40 controls). Quantitative real-time polymerase chain reaction (PCR) measured ERα messenger RNA (mRNA) in decidual tissue. Methylation-specific PCR was performed to analyze cytosine-phosphatidyl-guanine-island methylation of the ERα promoter.
Results:
Expression of ERα protein is upregulated (P = .011) in GDM in extravillous trophoblasts but not in syncytiotrophoblast. Gestational diabetes mellitus downregulated ERα in decidual vessels only in pregnancies with male but not female fetuses. Furthermore, mRNA of the ERα encoding gene estrogen receptor gene 1 (ESR1) was increased (+1.77 fold) in GDM decidua when compared to controls (P = .024). In parallel, the promoter of ESR1 was methylated only in decidua of healthy control individuals but not in GDM.
Conclusion:
Gestational diabetes mellitus affects expression of placental ERα in a cell type-dependent way, on epigenetic level. These data link GDM with epigenetic deregulations of ERα expression and open new insights into the intrauterine programming hypothesis of GDM.</description><identifier>ISSN: 1933-7191</identifier><identifier>EISSN: 1933-7205</identifier><identifier>DOI: 10.1177/1933719115585147</identifier><identifier>PMID: 25947892</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Adult ; Blood Vessels - metabolism ; Blood Vessels - pathology ; Case-Control Studies ; CpG Islands ; Diabetes, Gestational - genetics ; Diabetes, Gestational - metabolism ; Diabetes, Gestational - pathology ; DNA Methylation ; Down-Regulation ; Embryology ; Epigenesis, Genetic ; Estrogen Receptor alpha - genetics ; Estrogen Receptor alpha - metabolism ; Female ; Fetus - metabolism ; Gene Expression Regulation, Developmental ; Gestational Age ; Humans ; Immunohistochemistry ; Male ; Medicine & Public Health ; Obstetrics/Perinatology/Midwifery ; Original Article ; Placenta - blood supply ; Placenta - metabolism ; Placenta - pathology ; Pregnancy ; Promoter Regions, Genetic ; Real-Time Polymerase Chain Reaction ; Reproductive Medicine ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Sex Determination Processes ; Sex Factors ; Trophoblasts - metabolism ; Trophoblasts - pathology</subject><ispartof>Reproductive sciences (Thousand Oaks, Calif.), 2015-12, Vol.22 (12), p.1488-1495</ispartof><rights>The Author(s) 2015</rights><rights>Society for Reproductive Investigation 2015</rights><rights>The Author(s) 2015.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3367-9a70110ffda640af99a47250cea37ea12234e4ec70463081a8944ee4741bd5cb3</citedby><cites>FETCH-LOGICAL-c3367-9a70110ffda640af99a47250cea37ea12234e4ec70463081a8944ee4741bd5cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25947892$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Knabl, Julia</creatorcontrib><creatorcontrib>Hiden, Ursula</creatorcontrib><creatorcontrib>Hüttenbrenner, Rebecca</creatorcontrib><creatorcontrib>Riedel, Christina</creatorcontrib><creatorcontrib>Hutter, Stefan</creatorcontrib><creatorcontrib>Kirn, Verena</creatorcontrib><creatorcontrib>Günthner-Biller, Margit</creatorcontrib><creatorcontrib>Desoye, Gernot</creatorcontrib><creatorcontrib>Kainer, Franz</creatorcontrib><creatorcontrib>Jeschke, Udo</creatorcontrib><title>GDM Alters Expression of Placental Estrogen Receptor α in a Cell Type and Gender-Specific Manner</title><title>Reproductive sciences (Thousand Oaks, Calif.)</title><addtitle>Reprod. Sci</addtitle><addtitle>Reprod Sci</addtitle><description>Objective:
The nuclear receptor estrogen receptor α (ERα) is one of the key players in energy balance, insulin resistance, and trophoblast differentiation. We tested the hypothesis that gestational diabetes mellitus (GDM) alters expression of placental ERα in a cell type-specific manner and that this regulation may involve epigenetic changes.
Study Design:
Expression of ERα was analyzed by immunohistochemistry using the semiquantitative immunoreactive score in 80 placentas (40 GDM/40 controls). Quantitative real-time polymerase chain reaction (PCR) measured ERα messenger RNA (mRNA) in decidual tissue. Methylation-specific PCR was performed to analyze cytosine-phosphatidyl-guanine-island methylation of the ERα promoter.
Results:
Expression of ERα protein is upregulated (P = .011) in GDM in extravillous trophoblasts but not in syncytiotrophoblast. Gestational diabetes mellitus downregulated ERα in decidual vessels only in pregnancies with male but not female fetuses. Furthermore, mRNA of the ERα encoding gene estrogen receptor gene 1 (ESR1) was increased (+1.77 fold) in GDM decidua when compared to controls (P = .024). In parallel, the promoter of ESR1 was methylated only in decidua of healthy control individuals but not in GDM.
Conclusion:
Gestational diabetes mellitus affects expression of placental ERα in a cell type-dependent way, on epigenetic level. These data link GDM with epigenetic deregulations of ERα expression and open new insights into the intrauterine programming hypothesis of GDM.</description><subject>Adult</subject><subject>Blood Vessels - metabolism</subject><subject>Blood Vessels - pathology</subject><subject>Case-Control Studies</subject><subject>CpG Islands</subject><subject>Diabetes, Gestational - genetics</subject><subject>Diabetes, Gestational - metabolism</subject><subject>Diabetes, Gestational - pathology</subject><subject>DNA Methylation</subject><subject>Down-Regulation</subject><subject>Embryology</subject><subject>Epigenesis, Genetic</subject><subject>Estrogen Receptor alpha - genetics</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Female</subject><subject>Fetus - metabolism</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Gestational Age</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Medicine & Public Health</subject><subject>Obstetrics/Perinatology/Midwifery</subject><subject>Original Article</subject><subject>Placenta - blood supply</subject><subject>Placenta - metabolism</subject><subject>Placenta - pathology</subject><subject>Pregnancy</subject><subject>Promoter Regions, Genetic</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reproductive Medicine</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Sex Determination Processes</subject><subject>Sex Factors</subject><subject>Trophoblasts - metabolism</subject><subject>Trophoblasts - pathology</subject><issn>1933-7191</issn><issn>1933-7205</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqNkM9OwzAMxiMEYuPPnRPKkUshbtKlOU5jDCQQCMa58lJ36tSlJekk9li8CM9E0TYOHBAnW_bv-2R_jJ2BuATQ-gqMlBoMQJKkCSi9x_rfo0jHItnf9d2-x45CWAiRKBOnh6wXJ0bp1MR9hpPrBz6sWvKBj98bTyGUteN1wZ8qtORarPg4tL6ek-PPZKlpa88_P3jpOPIRVRWfrhvi6HI-IZeTj14asmVRWv6AzpE_YQcFVoFOt_WYvd6Mp6Pb6P5xcjca3kdWyoGODGoBIIoix4ESWBiDSseJsIRSE0IcS0WKrBZqIEUKmBqliJRWMMsTO5PH7GLj2_j6bUWhzZZlsN2B6KhehQy0lJCaAcQdKjao9XUInoqs8eUS_ToDkX0Hm_0OtpOcb91XsyXlP4Jdkh0AGyB0Kzcnny3qlXfdx3-ZRlsNzukf_Bf7Ho3R</recordid><startdate>20151201</startdate><enddate>20151201</enddate><creator>Knabl, Julia</creator><creator>Hiden, Ursula</creator><creator>Hüttenbrenner, Rebecca</creator><creator>Riedel, Christina</creator><creator>Hutter, Stefan</creator><creator>Kirn, Verena</creator><creator>Günthner-Biller, Margit</creator><creator>Desoye, Gernot</creator><creator>Kainer, Franz</creator><creator>Jeschke, Udo</creator><general>SAGE Publications</general><general>Springer International Publishing</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>20151201</creationdate><title>GDM Alters Expression of Placental Estrogen Receptor α in a Cell Type and Gender-Specific Manner</title><author>Knabl, Julia ; Hiden, Ursula ; Hüttenbrenner, Rebecca ; Riedel, Christina ; Hutter, Stefan ; Kirn, Verena ; Günthner-Biller, Margit ; Desoye, Gernot ; Kainer, Franz ; Jeschke, Udo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3367-9a70110ffda640af99a47250cea37ea12234e4ec70463081a8944ee4741bd5cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Blood Vessels - metabolism</topic><topic>Blood Vessels - pathology</topic><topic>Case-Control Studies</topic><topic>CpG Islands</topic><topic>Diabetes, Gestational - genetics</topic><topic>Diabetes, Gestational - metabolism</topic><topic>Diabetes, Gestational - pathology</topic><topic>DNA Methylation</topic><topic>Down-Regulation</topic><topic>Embryology</topic><topic>Epigenesis, Genetic</topic><topic>Estrogen Receptor alpha - genetics</topic><topic>Estrogen Receptor alpha - metabolism</topic><topic>Female</topic><topic>Fetus - metabolism</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Gestational Age</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Medicine & Public Health</topic><topic>Obstetrics/Perinatology/Midwifery</topic><topic>Original Article</topic><topic>Placenta - blood supply</topic><topic>Placenta - metabolism</topic><topic>Placenta - pathology</topic><topic>Pregnancy</topic><topic>Promoter Regions, Genetic</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Reproductive Medicine</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Sex Determination Processes</topic><topic>Sex Factors</topic><topic>Trophoblasts - metabolism</topic><topic>Trophoblasts - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Knabl, Julia</creatorcontrib><creatorcontrib>Hiden, Ursula</creatorcontrib><creatorcontrib>Hüttenbrenner, Rebecca</creatorcontrib><creatorcontrib>Riedel, Christina</creatorcontrib><creatorcontrib>Hutter, Stefan</creatorcontrib><creatorcontrib>Kirn, Verena</creatorcontrib><creatorcontrib>Günthner-Biller, Margit</creatorcontrib><creatorcontrib>Desoye, Gernot</creatorcontrib><creatorcontrib>Kainer, Franz</creatorcontrib><creatorcontrib>Jeschke, Udo</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>Reproductive sciences (Thousand Oaks, Calif.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Knabl, Julia</au><au>Hiden, Ursula</au><au>Hüttenbrenner, Rebecca</au><au>Riedel, Christina</au><au>Hutter, Stefan</au><au>Kirn, Verena</au><au>Günthner-Biller, Margit</au><au>Desoye, Gernot</au><au>Kainer, Franz</au><au>Jeschke, Udo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GDM Alters Expression of Placental Estrogen Receptor α in a Cell Type and Gender-Specific Manner</atitle><jtitle>Reproductive sciences (Thousand Oaks, Calif.)</jtitle><stitle>Reprod. Sci</stitle><addtitle>Reprod Sci</addtitle><date>2015-12-01</date><risdate>2015</risdate><volume>22</volume><issue>12</issue><spage>1488</spage><epage>1495</epage><pages>1488-1495</pages><issn>1933-7191</issn><eissn>1933-7205</eissn><abstract>Objective:
The nuclear receptor estrogen receptor α (ERα) is one of the key players in energy balance, insulin resistance, and trophoblast differentiation. We tested the hypothesis that gestational diabetes mellitus (GDM) alters expression of placental ERα in a cell type-specific manner and that this regulation may involve epigenetic changes.
Study Design:
Expression of ERα was analyzed by immunohistochemistry using the semiquantitative immunoreactive score in 80 placentas (40 GDM/40 controls). Quantitative real-time polymerase chain reaction (PCR) measured ERα messenger RNA (mRNA) in decidual tissue. Methylation-specific PCR was performed to analyze cytosine-phosphatidyl-guanine-island methylation of the ERα promoter.
Results:
Expression of ERα protein is upregulated (P = .011) in GDM in extravillous trophoblasts but not in syncytiotrophoblast. Gestational diabetes mellitus downregulated ERα in decidual vessels only in pregnancies with male but not female fetuses. Furthermore, mRNA of the ERα encoding gene estrogen receptor gene 1 (ESR1) was increased (+1.77 fold) in GDM decidua when compared to controls (P = .024). In parallel, the promoter of ESR1 was methylated only in decidua of healthy control individuals but not in GDM.
Conclusion:
Gestational diabetes mellitus affects expression of placental ERα in a cell type-dependent way, on epigenetic level. These data link GDM with epigenetic deregulations of ERα expression and open new insights into the intrauterine programming hypothesis of GDM.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>25947892</pmid><doi>10.1177/1933719115585147</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Reproductive sciences (Thousand Oaks, Calif.), 2015-12, Vol.22 (12), p.1488-1495 |
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| language | eng |
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| source | Springer Nature |
| subjects | Adult Blood Vessels - metabolism Blood Vessels - pathology Case-Control Studies CpG Islands Diabetes, Gestational - genetics Diabetes, Gestational - metabolism Diabetes, Gestational - pathology DNA Methylation Down-Regulation Embryology Epigenesis, Genetic Estrogen Receptor alpha - genetics Estrogen Receptor alpha - metabolism Female Fetus - metabolism Gene Expression Regulation, Developmental Gestational Age Humans Immunohistochemistry Male Medicine & Public Health Obstetrics/Perinatology/Midwifery Original Article Placenta - blood supply Placenta - metabolism Placenta - pathology Pregnancy Promoter Regions, Genetic Real-Time Polymerase Chain Reaction Reproductive Medicine Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism Sex Determination Processes Sex Factors Trophoblasts - metabolism Trophoblasts - pathology |
| title | GDM Alters Expression of Placental Estrogen Receptor α in a Cell Type and Gender-Specific Manner |
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