Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway

Prostaglandin E2 (PGE2) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE2 and exogenous PGE2, present at high concentration in seminal plasma. METHODS: This study investigated fib...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Human reproduction (Oxford) 2007, Vol.22 (1), p.36-44
Hauptverfasser: Battersby, S., Sales, K.J., Williams, A.R., Anderson, R.A., Gardner, S., Jabbour, H.N.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 44
container_issue 1
container_start_page 36
container_title Human reproduction (Oxford)
container_volume 22
creator Battersby, S.
Sales, K.J.
Williams, A.R.
Anderson, R.A.
Gardner, S.
Jabbour, H.N.
description Prostaglandin E2 (PGE2) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE2 and exogenous PGE2, present at high concentration in seminal plasma. METHODS: This study investigated fibroblast growth factor 2 (FGF2) mRNA expression and cell signalling in response to seminal plasma or PGE2, using an endometrial adenocarcinoma (Ishikawa) cell line stably expressing the EP2 receptor (EP2 sense cells) and endometrial adenocarcinoma explants. RESULTS: Seminal plasma and PGE2 induced a significant up-regulation of FGF2 expression in EP2 sense but not parental untransfected Ishikawa (wild-type) cells (P < 0.05). These effects were inhibited by co-treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src, epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via the EP2 receptor. Finally, seminal plasma and PGE2 significantly increased FGF2 mRNA expression in endometrial adenocarcinoma tissue explants via the EP2 receptor (P < 0.05). CONCLUSIONS: Seminal plasma and PGE2 can similarly activate FGF2 expression and EP2 receptor signalling in endometrial adenocarcinoma cells. These data highlight the potential for seminal plasma exposure to facilitate tumorigenesis–angiogenesis in endometrial adenocarcinomas in vivo.
doi_str_mv 10.1093/humrep/del328
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2694993</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/humrep/del328</oup_id><sourcerecordid>1180232631</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4568-1930acd2968dd7f9f67b31034b8ac2f558157d3832a8c3d3e3ef3c087cd041843</originalsourceid><addsrcrecordid>eNqFkktv1DAUhQMC0WFArNgiCwnEJtSPxHE2SKgaHlIlFsA68tg3My6JHWxn2v577jBDS9mwsiV_Puce-xTFc0bfMtqK0-08RphOLQyCq_vFglWSllzU9EGxoFyqkjHJTorHKV1QilslHxUnTLa0bmS9uPfsK4zO64FMg06jJtpbMsWQst4MuHeerDiZpzLCZh50BtK7dQxrhDPZxHCZt6TXJodIOIGrKUJKLniC98DbMEKODsW1BR-Mjsb5gCYGhiGRndNkVSaIDtLR0wdnS04iGJhQsxzBOjS1JEftE_q4nc57_dCTvAUCk7MQR3S4O8sfgd9x4Apv7y0xQCTJbTDuTR5LfmD8BGTSeXupr58UD3s9JHh6XJfF9w-rb2efyvMvHz-fvT8vTVXvH7UVVBvLW6msbfq2l81aMCqqtdKG93WtWN1YoQTXyggrQEAvDFWNsbRiqhLL4t1Bd5rXmNKAxyGHbopu1PG6C9p1d0-823absOu4bKu2FSjw-igQw88ZUu5Gl_YptYcwp04qIZsGG7IsXv4DXoQ54hukjjPM0fJaIVQeIIP_kCL0N5Mw2u171h161h16hvyLv8e_pY_FQuDVEdDJ6KHH_zMu3XIKTaVqkHtz4MI8_cfzF8BW9Fc</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>211939258</pqid></control><display><type>article</type><title>Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Oxford University Press Journals All Titles (1996-Current)</source><creator>Battersby, S. ; Sales, K.J. ; Williams, A.R. ; Anderson, R.A. ; Gardner, S. ; Jabbour, H.N.</creator><creatorcontrib>Battersby, S. ; Sales, K.J. ; Williams, A.R. ; Anderson, R.A. ; Gardner, S. ; Jabbour, H.N.</creatorcontrib><description>Prostaglandin E2 (PGE2) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE2 and exogenous PGE2, present at high concentration in seminal plasma. METHODS: This study investigated fibroblast growth factor 2 (FGF2) mRNA expression and cell signalling in response to seminal plasma or PGE2, using an endometrial adenocarcinoma (Ishikawa) cell line stably expressing the EP2 receptor (EP2 sense cells) and endometrial adenocarcinoma explants. RESULTS: Seminal plasma and PGE2 induced a significant up-regulation of FGF2 expression in EP2 sense but not parental untransfected Ishikawa (wild-type) cells (P &lt; 0.05). These effects were inhibited by co-treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src, epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via the EP2 receptor. Finally, seminal plasma and PGE2 significantly increased FGF2 mRNA expression in endometrial adenocarcinoma tissue explants via the EP2 receptor (P &lt; 0.05). CONCLUSIONS: Seminal plasma and PGE2 can similarly activate FGF2 expression and EP2 receptor signalling in endometrial adenocarcinoma cells. These data highlight the potential for seminal plasma exposure to facilitate tumorigenesis–angiogenesis in endometrial adenocarcinomas in vivo.</description><identifier>ISSN: 0268-1161</identifier><identifier>EISSN: 1460-2350</identifier><identifier>DOI: 10.1093/humrep/del328</identifier><identifier>PMID: 16905765</identifier><identifier>CODEN: HUREEE</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adenocarcinoma - metabolism ; Biological and medical sciences ; Cell Line, Tumor ; Cyclic AMP - metabolism ; Dinoprostone - physiology ; Endometrial Neoplasms - metabolism ; ErbB Receptors - physiology ; Extracellular Signal-Regulated MAP Kinases - physiology ; Female ; Fibroblast Growth Factor 2 - biosynthesis ; Gene Expression Regulation ; Gynecology. Andrology. Obstetrics ; Humans ; Male ; Medical sciences ; Microscopy, Confocal ; Microscopy, Fluorescence ; Phosphorylation - drug effects ; Proto-Oncogene Proteins pp60(c-src) - metabolism ; Receptors, Prostaglandin E - physiology ; Receptors, Prostaglandin E, EP2 Subtype ; Semen - physiology ; Signal Transduction ; Transcriptional Activation - physiology ; Up-Regulation</subject><ispartof>Human reproduction (Oxford), 2007, Vol.22 (1), p.36-44</ispartof><rights>The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org 2007</rights><rights>2007 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Jan 2007</rights><rights>The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4568-1930acd2968dd7f9f67b31034b8ac2f558157d3832a8c3d3e3ef3c087cd041843</citedby><cites>FETCH-LOGICAL-c4568-1930acd2968dd7f9f67b31034b8ac2f558157d3832a8c3d3e3ef3c087cd041843</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=18583687$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16905765$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Battersby, S.</creatorcontrib><creatorcontrib>Sales, K.J.</creatorcontrib><creatorcontrib>Williams, A.R.</creatorcontrib><creatorcontrib>Anderson, R.A.</creatorcontrib><creatorcontrib>Gardner, S.</creatorcontrib><creatorcontrib>Jabbour, H.N.</creatorcontrib><title>Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway</title><title>Human reproduction (Oxford)</title><addtitle>Hum Reprod</addtitle><addtitle>Hum Reprod</addtitle><description>Prostaglandin E2 (PGE2) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE2 and exogenous PGE2, present at high concentration in seminal plasma. METHODS: This study investigated fibroblast growth factor 2 (FGF2) mRNA expression and cell signalling in response to seminal plasma or PGE2, using an endometrial adenocarcinoma (Ishikawa) cell line stably expressing the EP2 receptor (EP2 sense cells) and endometrial adenocarcinoma explants. RESULTS: Seminal plasma and PGE2 induced a significant up-regulation of FGF2 expression in EP2 sense but not parental untransfected Ishikawa (wild-type) cells (P &lt; 0.05). These effects were inhibited by co-treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src, epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via the EP2 receptor. Finally, seminal plasma and PGE2 significantly increased FGF2 mRNA expression in endometrial adenocarcinoma tissue explants via the EP2 receptor (P &lt; 0.05). CONCLUSIONS: Seminal plasma and PGE2 can similarly activate FGF2 expression and EP2 receptor signalling in endometrial adenocarcinoma cells. These data highlight the potential for seminal plasma exposure to facilitate tumorigenesis–angiogenesis in endometrial adenocarcinomas in vivo.</description><subject>Adenocarcinoma - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cyclic AMP - metabolism</subject><subject>Dinoprostone - physiology</subject><subject>Endometrial Neoplasms - metabolism</subject><subject>ErbB Receptors - physiology</subject><subject>Extracellular Signal-Regulated MAP Kinases - physiology</subject><subject>Female</subject><subject>Fibroblast Growth Factor 2 - biosynthesis</subject><subject>Gene Expression Regulation</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microscopy, Confocal</subject><subject>Microscopy, Fluorescence</subject><subject>Phosphorylation - drug effects</subject><subject>Proto-Oncogene Proteins pp60(c-src) - metabolism</subject><subject>Receptors, Prostaglandin E - physiology</subject><subject>Receptors, Prostaglandin E, EP2 Subtype</subject><subject>Semen - physiology</subject><subject>Signal Transduction</subject><subject>Transcriptional Activation - physiology</subject><subject>Up-Regulation</subject><issn>0268-1161</issn><issn>1460-2350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktv1DAUhQMC0WFArNgiCwnEJtSPxHE2SKgaHlIlFsA68tg3My6JHWxn2v577jBDS9mwsiV_Puce-xTFc0bfMtqK0-08RphOLQyCq_vFglWSllzU9EGxoFyqkjHJTorHKV1QilslHxUnTLa0bmS9uPfsK4zO64FMg06jJtpbMsWQst4MuHeerDiZpzLCZh50BtK7dQxrhDPZxHCZt6TXJodIOIGrKUJKLniC98DbMEKODsW1BR-Mjsb5gCYGhiGRndNkVSaIDtLR0wdnS04iGJhQsxzBOjS1JEftE_q4nc57_dCTvAUCk7MQR3S4O8sfgd9x4Apv7y0xQCTJbTDuTR5LfmD8BGTSeXupr58UD3s9JHh6XJfF9w-rb2efyvMvHz-fvT8vTVXvH7UVVBvLW6msbfq2l81aMCqqtdKG93WtWN1YoQTXyggrQEAvDFWNsbRiqhLL4t1Bd5rXmNKAxyGHbopu1PG6C9p1d0-823absOu4bKu2FSjw-igQw88ZUu5Gl_YptYcwp04qIZsGG7IsXv4DXoQ54hukjjPM0fJaIVQeIIP_kCL0N5Mw2u171h161h16hvyLv8e_pY_FQuDVEdDJ6KHH_zMu3XIKTaVqkHtz4MI8_cfzF8BW9Fc</recordid><startdate>2007</startdate><enddate>2007</enddate><creator>Battersby, S.</creator><creator>Sales, K.J.</creator><creator>Williams, A.R.</creator><creator>Anderson, R.A.</creator><creator>Gardner, S.</creator><creator>Jabbour, H.N.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>IQODW</scope><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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>2007</creationdate><title>Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway</title><author>Battersby, S. ; Sales, K.J. ; Williams, A.R. ; Anderson, R.A. ; Gardner, S. ; Jabbour, H.N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4568-1930acd2968dd7f9f67b31034b8ac2f558157d3832a8c3d3e3ef3c087cd041843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adenocarcinoma - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cyclic AMP - metabolism</topic><topic>Dinoprostone - physiology</topic><topic>Endometrial Neoplasms - metabolism</topic><topic>ErbB Receptors - physiology</topic><topic>Extracellular Signal-Regulated MAP Kinases - physiology</topic><topic>Female</topic><topic>Fibroblast Growth Factor 2 - biosynthesis</topic><topic>Gene Expression Regulation</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microscopy, Confocal</topic><topic>Microscopy, Fluorescence</topic><topic>Phosphorylation - drug effects</topic><topic>Proto-Oncogene Proteins pp60(c-src) - metabolism</topic><topic>Receptors, Prostaglandin E - physiology</topic><topic>Receptors, Prostaglandin E, EP2 Subtype</topic><topic>Semen - physiology</topic><topic>Signal Transduction</topic><topic>Transcriptional Activation - physiology</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Battersby, S.</creatorcontrib><creatorcontrib>Sales, K.J.</creatorcontrib><creatorcontrib>Williams, A.R.</creatorcontrib><creatorcontrib>Anderson, R.A.</creatorcontrib><creatorcontrib>Gardner, S.</creatorcontrib><creatorcontrib>Jabbour, H.N.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human reproduction (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Battersby, S.</au><au>Sales, K.J.</au><au>Williams, A.R.</au><au>Anderson, R.A.</au><au>Gardner, S.</au><au>Jabbour, H.N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway</atitle><jtitle>Human reproduction (Oxford)</jtitle><stitle>Hum Reprod</stitle><addtitle>Hum Reprod</addtitle><date>2007</date><risdate>2007</risdate><volume>22</volume><issue>1</issue><spage>36</spage><epage>44</epage><pages>36-44</pages><issn>0268-1161</issn><eissn>1460-2350</eissn><coden>HUREEE</coden><abstract>Prostaglandin E2 (PGE2) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE2 and exogenous PGE2, present at high concentration in seminal plasma. METHODS: This study investigated fibroblast growth factor 2 (FGF2) mRNA expression and cell signalling in response to seminal plasma or PGE2, using an endometrial adenocarcinoma (Ishikawa) cell line stably expressing the EP2 receptor (EP2 sense cells) and endometrial adenocarcinoma explants. RESULTS: Seminal plasma and PGE2 induced a significant up-regulation of FGF2 expression in EP2 sense but not parental untransfected Ishikawa (wild-type) cells (P &lt; 0.05). These effects were inhibited by co-treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src, epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via the EP2 receptor. Finally, seminal plasma and PGE2 significantly increased FGF2 mRNA expression in endometrial adenocarcinoma tissue explants via the EP2 receptor (P &lt; 0.05). CONCLUSIONS: Seminal plasma and PGE2 can similarly activate FGF2 expression and EP2 receptor signalling in endometrial adenocarcinoma cells. These data highlight the potential for seminal plasma exposure to facilitate tumorigenesis–angiogenesis in endometrial adenocarcinomas in vivo.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>16905765</pmid><doi>10.1093/humrep/del328</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0268-1161
ispartof Human reproduction (Oxford), 2007, Vol.22 (1), p.36-44
issn 0268-1161
1460-2350
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2694993
source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current)
subjects Adenocarcinoma - metabolism
Biological and medical sciences
Cell Line, Tumor
Cyclic AMP - metabolism
Dinoprostone - physiology
Endometrial Neoplasms - metabolism
ErbB Receptors - physiology
Extracellular Signal-Regulated MAP Kinases - physiology
Female
Fibroblast Growth Factor 2 - biosynthesis
Gene Expression Regulation
Gynecology. Andrology. Obstetrics
Humans
Male
Medical sciences
Microscopy, Confocal
Microscopy, Fluorescence
Phosphorylation - drug effects
Proto-Oncogene Proteins pp60(c-src) - metabolism
Receptors, Prostaglandin E - physiology
Receptors, Prostaglandin E, EP2 Subtype
Semen - physiology
Signal Transduction
Transcriptional Activation - physiology
Up-Regulation
title Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T12%3A57%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Seminal%20plasma%20and%20prostaglandin%20E2%20up-regulate%20fibroblast%20growth%20factor%202%20expression%20in%20endometrial%20adenocarcinoma%20cells%20via%20E-series%20prostanoid-2%20receptor-mediated%20transactivation%20of%20the%20epidermal%20growth%20factor%20receptor%20and%20extracellular%20signal-regulated%20kinase%20pathway&rft.jtitle=Human%20reproduction%20(Oxford)&rft.au=Battersby,%20S.&rft.date=2007&rft.volume=22&rft.issue=1&rft.spage=36&rft.epage=44&rft.pages=36-44&rft.issn=0268-1161&rft.eissn=1460-2350&rft.coden=HUREEE&rft_id=info:doi/10.1093/humrep/del328&rft_dat=%3Cproquest_pubme%3E1180232631%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=211939258&rft_id=info:pmid/16905765&rft_oup_id=10.1093/humrep/del328&rfr_iscdi=true