Signal transducer and activator of transcription‐3 (Stat3) plays a critical role in implantation via progesterone receptor in uterus
Recent studies have shown that activation of the signal transducer and activator of transcription‐3 (Stat3) is required for decidualization, interacting with progesterone receptor (PR) in uterus. Based on previous reports, we hypothesized that crosstalk between STAT3 and PR signaling is required for...
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| Veröffentlicht in: | The FASEB journal 2013-07, Vol.27 (7), p.2553-2563 |
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| creator | Lee, Jae Hee Kim, Tae Hoon Oh, Seo Jin Yoo, Jung‐Yoon Akira, Shizuo Ku, Bon Jeong Lydon, John P. Jeong, Jae‐Wook |
| description | Recent studies have shown that activation of the signal transducer and activator of transcription‐3 (Stat3) is required for decidualization, interacting with progesterone receptor (PR) in uterus. Based on previous reports, we hypothesized that crosstalk between STAT3 and PR signaling is required for successful implantation. To identify the interaction between STAT3 and PR isoforms, we performed immunoprecipitation following transient cotransfection and found that STAT3 physically interacted with PR‐A, which is known to be important for uterine development and function, but not with PR‐B. To further investigate the role of Stat3 in uterine function, Stat3 was conditionally ablated only in the PR‐positive cells (PRcre/+ Stat3f/f; Stat3d/d). Our studies revealed that ovarian function and uterine development of Stat3d/d mice were normal. However, Stat3d/d female mice were infertile due to defective embryo implantation. Unlike Stat3f/f mice, Stat3d/d mice exhibited an unclosed uterine lumen. Furthermore, uteri of Stat3d/d mice were unable to undergo a well‐characterized hormonally induced decidual reaction. The expression of stromal PR was decreased during decidualization and preimplantation period in Stat3d/d mice, and PR target genes were significantly down‐regulated after progesterone induction. Our results suggest that STAT3 and PR crosstalk is required for successful implantation in the mouse uterus.—Lee, J. H., Kim, T. H., Oh, S. J., Yoo, J.‐Y., Akira, S., Ku, B. J., Lydon, J. P., Jeong, J.‐W. Signal transducer and activator of transcription‐3 (Stat3) plays a critical role in implantation via progesterone receptor in uterus. FASEB J. 27, 2553–2563 (2013). www.fasebj.org |
| doi_str_mv | 10.1096/fj.12-225664 |
| format | Article |
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Based on previous reports, we hypothesized that crosstalk between STAT3 and PR signaling is required for successful implantation. To identify the interaction between STAT3 and PR isoforms, we performed immunoprecipitation following transient cotransfection and found that STAT3 physically interacted with PR‐A, which is known to be important for uterine development and function, but not with PR‐B. To further investigate the role of Stat3 in uterine function, Stat3 was conditionally ablated only in the PR‐positive cells (PRcre/+ Stat3f/f; Stat3d/d). Our studies revealed that ovarian function and uterine development of Stat3d/d mice were normal. However, Stat3d/d female mice were infertile due to defective embryo implantation. Unlike Stat3f/f mice, Stat3d/d mice exhibited an unclosed uterine lumen. Furthermore, uteri of Stat3d/d mice were unable to undergo a well‐characterized hormonally induced decidual reaction. The expression of stromal PR was decreased during decidualization and preimplantation period in Stat3d/d mice, and PR target genes were significantly down‐regulated after progesterone induction. Our results suggest that STAT3 and PR crosstalk is required for successful implantation in the mouse uterus.—Lee, J. H., Kim, T. H., Oh, S. J., Yoo, J.‐Y., Akira, S., Ku, B. J., Lydon, J. P., Jeong, J.‐W. Signal transducer and activator of transcription‐3 (Stat3) plays a critical role in implantation via progesterone receptor in uterus. FASEB J. 27, 2553–2563 (2013). www.fasebj.org</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.12-225664</identifier><identifier>PMID: 23531596</identifier><language>eng</language><publisher>Bethesda, MD, USA: Federation of American Societies for Experimental Biology</publisher><subject>animal model ; Animals ; Decidua - metabolism ; Decidua - physiology ; early pregnancy ; Embryo Implantation - genetics ; Embryo Implantation - physiology ; Female ; Fertility - genetics ; Fertility - physiology ; Gene Expression Regulation, Developmental - drug effects ; HEK293 Cells ; Humans ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pregnancy ; Progesterone - pharmacology ; Protein Binding ; Receptors, Progesterone - genetics ; Receptors, Progesterone - metabolism ; Receptors, Progesterone - physiology ; Research Communications ; Reverse Transcriptase Polymerase Chain Reaction ; STAT3 Transcription Factor - genetics ; STAT3 Transcription Factor - metabolism ; STAT3 Transcription Factor - physiology ; steroid hormone ; transcription factor ; Uterus - metabolism ; Uterus - physiology</subject><ispartof>The FASEB journal, 2013-07, Vol.27 (7), p.2553-2563</ispartof><rights>FASEB</rights><rights>FASEB 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4275-d10884f867752ddc2f9b87c2bc453698d1a7aeb4fb32b2ab57c981cb11709dc03</citedby><cites>FETCH-LOGICAL-c4275-d10884f867752ddc2f9b87c2bc453698d1a7aeb4fb32b2ab57c981cb11709dc03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.12-225664$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.12-225664$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23531596$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Jae Hee</creatorcontrib><creatorcontrib>Kim, Tae Hoon</creatorcontrib><creatorcontrib>Oh, Seo Jin</creatorcontrib><creatorcontrib>Yoo, Jung‐Yoon</creatorcontrib><creatorcontrib>Akira, Shizuo</creatorcontrib><creatorcontrib>Ku, Bon Jeong</creatorcontrib><creatorcontrib>Lydon, John P.</creatorcontrib><creatorcontrib>Jeong, Jae‐Wook</creatorcontrib><title>Signal transducer and activator of transcription‐3 (Stat3) plays a critical role in implantation via progesterone receptor in uterus</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>Recent studies have shown that activation of the signal transducer and activator of transcription‐3 (Stat3) is required for decidualization, interacting with progesterone receptor (PR) in uterus. Based on previous reports, we hypothesized that crosstalk between STAT3 and PR signaling is required for successful implantation. To identify the interaction between STAT3 and PR isoforms, we performed immunoprecipitation following transient cotransfection and found that STAT3 physically interacted with PR‐A, which is known to be important for uterine development and function, but not with PR‐B. To further investigate the role of Stat3 in uterine function, Stat3 was conditionally ablated only in the PR‐positive cells (PRcre/+ Stat3f/f; Stat3d/d). Our studies revealed that ovarian function and uterine development of Stat3d/d mice were normal. However, Stat3d/d female mice were infertile due to defective embryo implantation. Unlike Stat3f/f mice, Stat3d/d mice exhibited an unclosed uterine lumen. Furthermore, uteri of Stat3d/d mice were unable to undergo a well‐characterized hormonally induced decidual reaction. The expression of stromal PR was decreased during decidualization and preimplantation period in Stat3d/d mice, and PR target genes were significantly down‐regulated after progesterone induction. Our results suggest that STAT3 and PR crosstalk is required for successful implantation in the mouse uterus.—Lee, J. H., Kim, T. H., Oh, S. J., Yoo, J.‐Y., Akira, S., Ku, B. J., Lydon, J. P., Jeong, J.‐W. Signal transducer and activator of transcription‐3 (Stat3) plays a critical role in implantation via progesterone receptor in uterus. 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Based on previous reports, we hypothesized that crosstalk between STAT3 and PR signaling is required for successful implantation. To identify the interaction between STAT3 and PR isoforms, we performed immunoprecipitation following transient cotransfection and found that STAT3 physically interacted with PR‐A, which is known to be important for uterine development and function, but not with PR‐B. To further investigate the role of Stat3 in uterine function, Stat3 was conditionally ablated only in the PR‐positive cells (PRcre/+ Stat3f/f; Stat3d/d). Our studies revealed that ovarian function and uterine development of Stat3d/d mice were normal. However, Stat3d/d female mice were infertile due to defective embryo implantation. Unlike Stat3f/f mice, Stat3d/d mice exhibited an unclosed uterine lumen. Furthermore, uteri of Stat3d/d mice were unable to undergo a well‐characterized hormonally induced decidual reaction. The expression of stromal PR was decreased during decidualization and preimplantation period in Stat3d/d mice, and PR target genes were significantly down‐regulated after progesterone induction. Our results suggest that STAT3 and PR crosstalk is required for successful implantation in the mouse uterus.—Lee, J. H., Kim, T. H., Oh, S. J., Yoo, J.‐Y., Akira, S., Ku, B. J., Lydon, J. P., Jeong, J.‐W. Signal transducer and activator of transcription‐3 (Stat3) plays a critical role in implantation via progesterone receptor in uterus. FASEB J. 27, 2553–2563 (2013). www.fasebj.org</abstract><cop>Bethesda, MD, USA</cop><pub>Federation of American Societies for Experimental Biology</pub><pmid>23531596</pmid><doi>10.1096/fj.12-225664</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | animal model Animals Decidua - metabolism Decidua - physiology early pregnancy Embryo Implantation - genetics Embryo Implantation - physiology Female Fertility - genetics Fertility - physiology Gene Expression Regulation, Developmental - drug effects HEK293 Cells Humans Immunohistochemistry Male Mice Mice, Inbred C57BL Mice, Knockout Pregnancy Progesterone - pharmacology Protein Binding Receptors, Progesterone - genetics Receptors, Progesterone - metabolism Receptors, Progesterone - physiology Research Communications Reverse Transcriptase Polymerase Chain Reaction STAT3 Transcription Factor - genetics STAT3 Transcription Factor - metabolism STAT3 Transcription Factor - physiology steroid hormone transcription factor Uterus - metabolism Uterus - physiology |
| title | Signal transducer and activator of transcription‐3 (Stat3) plays a critical role in implantation via progesterone receptor in uterus |
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