Loss of WT1 Expression in the Endometrium of Infertile PCOS Patients: A Hyperandrogenic Effect?
Context: In fertile patients the endometrial Wilms tumor suppressor gene (WT1) is expressed during the window of implantation. Polycystic ovary syndrome (PCOS) patients suffer from hyperandrogenemia and infertility and have elevated endometrial androgen receptor (AR) expression. WT1 is known to be d...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2012-03, Vol.97 (3), p.957-966 |
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| container_title | The journal of clinical endocrinology and metabolism |
| container_volume | 97 |
| creator | Gonzalez, D Thackeray, H Lewis, P. D Mantani, A Brook, N Ahuja, K Margara, R Joels, L White, J. O Conlan, R. S |
| description | Context:
In fertile patients the endometrial Wilms tumor suppressor gene (WT1) is expressed during the window of implantation. Polycystic ovary syndrome (PCOS) patients suffer from hyperandrogenemia and infertility and have elevated endometrial androgen receptor (AR) expression. WT1 is known to be down-regulated by AR. Therefore, the expression of WT1 and its targets may be altered in PCOS endometrium.
Objective:
The objective of the study was to assess the expression and regulation of WT1 and selected downstream targets in secretory endometrium from ovulatory PCOS (ovPCOS) and fertile women.
Design and Patients:
Endometrial samples were obtained from 25 ovPCOS and 25 fertile patients.
Main Outcome Measure:
Endometrial expression of WT1 and selected downstream targets were assessed by immunohistochemistry and RT-PCR. The androgen effect on WT1 expression was determined in vitro by immunoblots and RT-PCR. The expression of WT1 and its targets was quantified in fertile and ovPCOS stromal cells in the presence of androgens by RT-PCR. Caspase-3/7 activity was measured to evaluate sensitivity to drug-induced apoptosis.
Results:
WT1 expression was down-regulated in secretory-phase ovPCOS endometrium. Stromal expression of Bcl-2 and p27 was higher, and epidermal growth factor receptor was lower in ovPCOS than in fertile patients. Endometrial stromal expression of WT1, Bcl-2, Bcl-2-associated X protein, and β-catenin was regulated by androgens. Apoptosis levels were reduced in ovPCOS samples and androgen-treated fertile samples.
Conclusion:
WT1 expression is down-regulated in ovPCOS endometrium during the window of implantation. Androgens regulate the expression of WT1 and its targets during endometrial decidualization. The altered balance between WT1 and AR in the endometrium of PCOS patients may jeopardize the success of decidualization and endometrial receptivity. |
| doi_str_mv | 10.1210/jc.2011-2366 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_926644207</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>926644207</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4477-b4f76ccbacda6736cda5a09067a08edcfc9195069b309694015c8977251df6ca3</originalsourceid><addsrcrecordid>eNptkc9rFDEUgIModlu9eZZcxItT82uSiRcpy9YWFlqworeQzby4WWcy22SG2v_ejLvqxcDjEfjy8t73EHpFyTlllLzfuXNGKK0Yl_IJWlAt6kpRrZ6iBSGMVlqxbyfoNOcdIVSImj9HJ4wx3gjCF8ish5zx4PHXO4pXP_cJcg5DxCHicQt4FduhhzGFqZ-h6-ghjaEDfLu8-Yxv7RggjvkDvsBXj3tINrZp-A4xOLzyHtz48QV65m2X4eUxn6Evl6u75VW1vvl0vbxYV04IpaqN8Eo6t7GutVJxWVJtiSZSWdJA67zTVNdE6g0nWmpBaO0arRSraeuls_wMvT3U3afhfoI8mj5kB11nIwxTNppJKQQjqpDvDqRLZfQE3uxT6G16NJSY2ajZOTMbNbPRgr8-Fp42PbR_4T8KC_DmCNjsbOeLBBfyP66WhIimLpw4cA9DN0LKP7rpAZLZgu3GrSHlCKmaqvzMCC-3qgSf2-WHZ1BW4VKI8HtHZjdMKRaj_-_6FyW1nWo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>926644207</pqid></control><display><type>article</type><title>Loss of WT1 Expression in the Endometrium of Infertile PCOS Patients: A Hyperandrogenic Effect?</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><source>Journals@Ovid Complete</source><creator>Gonzalez, D ; Thackeray, H ; Lewis, P. D ; Mantani, A ; Brook, N ; Ahuja, K ; Margara, R ; Joels, L ; White, J. O ; Conlan, R. S</creator><creatorcontrib>Gonzalez, D ; Thackeray, H ; Lewis, P. D ; Mantani, A ; Brook, N ; Ahuja, K ; Margara, R ; Joels, L ; White, J. O ; Conlan, R. S</creatorcontrib><description>Context:
In fertile patients the endometrial Wilms tumor suppressor gene (WT1) is expressed during the window of implantation. Polycystic ovary syndrome (PCOS) patients suffer from hyperandrogenemia and infertility and have elevated endometrial androgen receptor (AR) expression. WT1 is known to be down-regulated by AR. Therefore, the expression of WT1 and its targets may be altered in PCOS endometrium.
Objective:
The objective of the study was to assess the expression and regulation of WT1 and selected downstream targets in secretory endometrium from ovulatory PCOS (ovPCOS) and fertile women.
Design and Patients:
Endometrial samples were obtained from 25 ovPCOS and 25 fertile patients.
Main Outcome Measure:
Endometrial expression of WT1 and selected downstream targets were assessed by immunohistochemistry and RT-PCR. The androgen effect on WT1 expression was determined in vitro by immunoblots and RT-PCR. The expression of WT1 and its targets was quantified in fertile and ovPCOS stromal cells in the presence of androgens by RT-PCR. Caspase-3/7 activity was measured to evaluate sensitivity to drug-induced apoptosis.
Results:
WT1 expression was down-regulated in secretory-phase ovPCOS endometrium. Stromal expression of Bcl-2 and p27 was higher, and epidermal growth factor receptor was lower in ovPCOS than in fertile patients. Endometrial stromal expression of WT1, Bcl-2, Bcl-2-associated X protein, and β-catenin was regulated by androgens. Apoptosis levels were reduced in ovPCOS samples and androgen-treated fertile samples.
Conclusion:
WT1 expression is down-regulated in ovPCOS endometrium during the window of implantation. Androgens regulate the expression of WT1 and its targets during endometrial decidualization. The altered balance between WT1 and AR in the endometrium of PCOS patients may jeopardize the success of decidualization and endometrial receptivity.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2011-2366</identifier><identifier>PMID: 22238403</identifier><identifier>CODEN: JCEMAZ</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Adult ; Biological and medical sciences ; Caspase 3 - genetics ; Caspase 3 - metabolism ; Caspase 7 - genetics ; Caspase 7 - metabolism ; Endocrinopathies ; Endometrium - metabolism ; Feeding. Feeding behavior ; Female ; Fundamental and applied biological sciences. Psychology ; Humans ; Hyperandrogenism - genetics ; Hyperandrogenism - metabolism ; Infertility, Female - genetics ; Infertility, Female - metabolism ; Medical sciences ; Polycystic Ovary Syndrome - genetics ; Polycystic Ovary Syndrome - metabolism ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; Vertebrates: endocrinology ; WT1 Proteins - genetics ; WT1 Proteins - metabolism</subject><ispartof>The journal of clinical endocrinology and metabolism, 2012-03, Vol.97 (3), p.957-966</ispartof><rights>Copyright © 2012 by The Endocrine Society</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4477-b4f76ccbacda6736cda5a09067a08edcfc9195069b309694015c8977251df6ca3</citedby><cites>FETCH-LOGICAL-c4477-b4f76ccbacda6736cda5a09067a08edcfc9195069b309694015c8977251df6ca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25600485$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22238403$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gonzalez, D</creatorcontrib><creatorcontrib>Thackeray, H</creatorcontrib><creatorcontrib>Lewis, P. D</creatorcontrib><creatorcontrib>Mantani, A</creatorcontrib><creatorcontrib>Brook, N</creatorcontrib><creatorcontrib>Ahuja, K</creatorcontrib><creatorcontrib>Margara, R</creatorcontrib><creatorcontrib>Joels, L</creatorcontrib><creatorcontrib>White, J. O</creatorcontrib><creatorcontrib>Conlan, R. S</creatorcontrib><title>Loss of WT1 Expression in the Endometrium of Infertile PCOS Patients: A Hyperandrogenic Effect?</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Context:
In fertile patients the endometrial Wilms tumor suppressor gene (WT1) is expressed during the window of implantation. Polycystic ovary syndrome (PCOS) patients suffer from hyperandrogenemia and infertility and have elevated endometrial androgen receptor (AR) expression. WT1 is known to be down-regulated by AR. Therefore, the expression of WT1 and its targets may be altered in PCOS endometrium.
Objective:
The objective of the study was to assess the expression and regulation of WT1 and selected downstream targets in secretory endometrium from ovulatory PCOS (ovPCOS) and fertile women.
Design and Patients:
Endometrial samples were obtained from 25 ovPCOS and 25 fertile patients.
Main Outcome Measure:
Endometrial expression of WT1 and selected downstream targets were assessed by immunohistochemistry and RT-PCR. The androgen effect on WT1 expression was determined in vitro by immunoblots and RT-PCR. The expression of WT1 and its targets was quantified in fertile and ovPCOS stromal cells in the presence of androgens by RT-PCR. Caspase-3/7 activity was measured to evaluate sensitivity to drug-induced apoptosis.
Results:
WT1 expression was down-regulated in secretory-phase ovPCOS endometrium. Stromal expression of Bcl-2 and p27 was higher, and epidermal growth factor receptor was lower in ovPCOS than in fertile patients. Endometrial stromal expression of WT1, Bcl-2, Bcl-2-associated X protein, and β-catenin was regulated by androgens. Apoptosis levels were reduced in ovPCOS samples and androgen-treated fertile samples.
Conclusion:
WT1 expression is down-regulated in ovPCOS endometrium during the window of implantation. Androgens regulate the expression of WT1 and its targets during endometrial decidualization. The altered balance between WT1 and AR in the endometrium of PCOS patients may jeopardize the success of decidualization and endometrial receptivity.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Caspase 3 - genetics</subject><subject>Caspase 3 - metabolism</subject><subject>Caspase 7 - genetics</subject><subject>Caspase 7 - metabolism</subject><subject>Endocrinopathies</subject><subject>Endometrium - metabolism</subject><subject>Feeding. Feeding behavior</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Hyperandrogenism - genetics</subject><subject>Hyperandrogenism - metabolism</subject><subject>Infertility, Female - genetics</subject><subject>Infertility, Female - metabolism</subject><subject>Medical sciences</subject><subject>Polycystic Ovary Syndrome - genetics</subject><subject>Polycystic Ovary Syndrome - metabolism</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>Vertebrates: endocrinology</subject><subject>WT1 Proteins - genetics</subject><subject>WT1 Proteins - metabolism</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkc9rFDEUgIModlu9eZZcxItT82uSiRcpy9YWFlqworeQzby4WWcy22SG2v_ejLvqxcDjEfjy8t73EHpFyTlllLzfuXNGKK0Yl_IJWlAt6kpRrZ6iBSGMVlqxbyfoNOcdIVSImj9HJ4wx3gjCF8ish5zx4PHXO4pXP_cJcg5DxCHicQt4FduhhzGFqZ-h6-ghjaEDfLu8-Yxv7RggjvkDvsBXj3tINrZp-A4xOLzyHtz48QV65m2X4eUxn6Evl6u75VW1vvl0vbxYV04IpaqN8Eo6t7GutVJxWVJtiSZSWdJA67zTVNdE6g0nWmpBaO0arRSraeuls_wMvT3U3afhfoI8mj5kB11nIwxTNppJKQQjqpDvDqRLZfQE3uxT6G16NJSY2ajZOTMbNbPRgr8-Fp42PbR_4T8KC_DmCNjsbOeLBBfyP66WhIimLpw4cA9DN0LKP7rpAZLZgu3GrSHlCKmaqvzMCC-3qgSf2-WHZ1BW4VKI8HtHZjdMKRaj_-_6FyW1nWo</recordid><startdate>201203</startdate><enddate>201203</enddate><creator>Gonzalez, D</creator><creator>Thackeray, H</creator><creator>Lewis, P. D</creator><creator>Mantani, A</creator><creator>Brook, N</creator><creator>Ahuja, K</creator><creator>Margara, R</creator><creator>Joels, L</creator><creator>White, J. O</creator><creator>Conlan, R. S</creator><general>Endocrine Society</general><general>Copyright by The Endocrine Society</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>7X8</scope></search><sort><creationdate>201203</creationdate><title>Loss of WT1 Expression in the Endometrium of Infertile PCOS Patients: A Hyperandrogenic Effect?</title><author>Gonzalez, D ; Thackeray, H ; Lewis, P. D ; Mantani, A ; Brook, N ; Ahuja, K ; Margara, R ; Joels, L ; White, J. O ; Conlan, R. S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4477-b4f76ccbacda6736cda5a09067a08edcfc9195069b309694015c8977251df6ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Caspase 3 - genetics</topic><topic>Caspase 3 - metabolism</topic><topic>Caspase 7 - genetics</topic><topic>Caspase 7 - metabolism</topic><topic>Endocrinopathies</topic><topic>Endometrium - metabolism</topic><topic>Feeding. Feeding behavior</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Hyperandrogenism - genetics</topic><topic>Hyperandrogenism - metabolism</topic><topic>Infertility, Female - genetics</topic><topic>Infertility, Female - metabolism</topic><topic>Medical sciences</topic><topic>Polycystic Ovary Syndrome - genetics</topic><topic>Polycystic Ovary Syndrome - metabolism</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>Vertebrates: endocrinology</topic><topic>WT1 Proteins - genetics</topic><topic>WT1 Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gonzalez, D</creatorcontrib><creatorcontrib>Thackeray, H</creatorcontrib><creatorcontrib>Lewis, P. D</creatorcontrib><creatorcontrib>Mantani, A</creatorcontrib><creatorcontrib>Brook, N</creatorcontrib><creatorcontrib>Ahuja, K</creatorcontrib><creatorcontrib>Margara, R</creatorcontrib><creatorcontrib>Joels, L</creatorcontrib><creatorcontrib>White, J. O</creatorcontrib><creatorcontrib>Conlan, R. S</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>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gonzalez, D</au><au>Thackeray, H</au><au>Lewis, P. D</au><au>Mantani, A</au><au>Brook, N</au><au>Ahuja, K</au><au>Margara, R</au><au>Joels, L</au><au>White, J. O</au><au>Conlan, R. S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of WT1 Expression in the Endometrium of Infertile PCOS Patients: A Hyperandrogenic Effect?</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2012-03</date><risdate>2012</risdate><volume>97</volume><issue>3</issue><spage>957</spage><epage>966</epage><pages>957-966</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>Context:
In fertile patients the endometrial Wilms tumor suppressor gene (WT1) is expressed during the window of implantation. Polycystic ovary syndrome (PCOS) patients suffer from hyperandrogenemia and infertility and have elevated endometrial androgen receptor (AR) expression. WT1 is known to be down-regulated by AR. Therefore, the expression of WT1 and its targets may be altered in PCOS endometrium.
Objective:
The objective of the study was to assess the expression and regulation of WT1 and selected downstream targets in secretory endometrium from ovulatory PCOS (ovPCOS) and fertile women.
Design and Patients:
Endometrial samples were obtained from 25 ovPCOS and 25 fertile patients.
Main Outcome Measure:
Endometrial expression of WT1 and selected downstream targets were assessed by immunohistochemistry and RT-PCR. The androgen effect on WT1 expression was determined in vitro by immunoblots and RT-PCR. The expression of WT1 and its targets was quantified in fertile and ovPCOS stromal cells in the presence of androgens by RT-PCR. Caspase-3/7 activity was measured to evaluate sensitivity to drug-induced apoptosis.
Results:
WT1 expression was down-regulated in secretory-phase ovPCOS endometrium. Stromal expression of Bcl-2 and p27 was higher, and epidermal growth factor receptor was lower in ovPCOS than in fertile patients. Endometrial stromal expression of WT1, Bcl-2, Bcl-2-associated X protein, and β-catenin was regulated by androgens. Apoptosis levels were reduced in ovPCOS samples and androgen-treated fertile samples.
Conclusion:
WT1 expression is down-regulated in ovPCOS endometrium during the window of implantation. Androgens regulate the expression of WT1 and its targets during endometrial decidualization. The altered balance between WT1 and AR in the endometrium of PCOS patients may jeopardize the success of decidualization and endometrial receptivity.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>22238403</pmid><doi>10.1210/jc.2011-2366</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The journal of clinical endocrinology and metabolism, 2012-03, Vol.97 (3), p.957-966 |
| issn | 0021-972X 1945-7197 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_926644207 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Journals@Ovid Complete |
| subjects | Adult Biological and medical sciences Caspase 3 - genetics Caspase 3 - metabolism Caspase 7 - genetics Caspase 7 - metabolism Endocrinopathies Endometrium - metabolism Feeding. Feeding behavior Female Fundamental and applied biological sciences. Psychology Humans Hyperandrogenism - genetics Hyperandrogenism - metabolism Infertility, Female - genetics Infertility, Female - metabolism Medical sciences Polycystic Ovary Syndrome - genetics Polycystic Ovary Syndrome - metabolism Vertebrates: anatomy and physiology, studies on body, several organs or systems Vertebrates: endocrinology WT1 Proteins - genetics WT1 Proteins - metabolism |
| title | Loss of WT1 Expression in the Endometrium of Infertile PCOS Patients: A Hyperandrogenic Effect? |
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