Activation of cumulus cell SMAD2/3 and epidermal growth factor receptor pathways are involved in porcine oocyte-cumulus cell expansion and steroidogenesis
Several lines of evidence suggest that in mice the activation of SMAD2/3 signaling by oocyte secreted factors, together with epidermal growth factor receptor (EGFR) activation, is essential to induce cumulus expansion. Here we show that inhibition of EGFR kinase in follicle stimulating hormone (FSH)...
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| Veröffentlicht in: | Molecular reproduction and development 2011-06, Vol.78 (6), p.391-402 |
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| creator | Nagyova, Eva Camaioni, Antonella Scsukova, Sona Mlynarcikova, Alzbeta Prochazka, Radek Nemcova, Lucie Salustri, Antonietta |
| description | Several lines of evidence suggest that in mice the activation of SMAD2/3 signaling by oocyte secreted factors, together with epidermal growth factor receptor (EGFR) activation, is essential to induce cumulus expansion. Here we show that inhibition of EGFR kinase in follicle stimulating hormone (FSH)‐stimulated porcine oocyte–cumulus cell complex (OCCs) strongly decreases hyaluronan (HA) synthesis and its retention in the matrix, as well as progesterone synthesis. Although porcine cumulus cells undergo expansion independently of oocytes, we use biochemical and gene expression analyses to show that they do require activation of SMAD2/3 for optimal stimulation of HA synthesis and proteins involved in the organization of this polymer in the expanded matrix. Furthermore, FSH‐induced progesterone synthesis by porcine cumulus cells was increased by blocking SMAD2/3 activation. In conclusion, these results support the hypothesis that an FSH–EGF autocrine loop is active in porcine OCCs, and provide the first evidence that the SMAD2/3 signaling pathway is induced by paracrine/autocrine factors in porcine cumulus cells and is involved in the control of both cumulus expansion and steroidogenesis. Mol. Reprod. Dev. 78:391–402, 2011. © 2011 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/mrd.21312 |
| format | Article |
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Here we show that inhibition of EGFR kinase in follicle stimulating hormone (FSH)‐stimulated porcine oocyte–cumulus cell complex (OCCs) strongly decreases hyaluronan (HA) synthesis and its retention in the matrix, as well as progesterone synthesis. Although porcine cumulus cells undergo expansion independently of oocytes, we use biochemical and gene expression analyses to show that they do require activation of SMAD2/3 for optimal stimulation of HA synthesis and proteins involved in the organization of this polymer in the expanded matrix. Furthermore, FSH‐induced progesterone synthesis by porcine cumulus cells was increased by blocking SMAD2/3 activation. In conclusion, these results support the hypothesis that an FSH–EGF autocrine loop is active in porcine OCCs, and provide the first evidence that the SMAD2/3 signaling pathway is induced by paracrine/autocrine factors in porcine cumulus cells and is involved in the control of both cumulus expansion and steroidogenesis. Mol. Reprod. Dev. 78:391–402, 2011. © 2011 Wiley‐Liss, Inc.</description><identifier>ISSN: 1040-452X</identifier><identifier>EISSN: 1098-2795</identifier><identifier>DOI: 10.1002/mrd.21312</identifier><identifier>PMID: 21520325</identifier><identifier>CODEN: MREDEE</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Benzamides - pharmacology ; Biological and medical sciences ; C-Reactive Protein - metabolism ; Cell Adhesion Molecules - antagonists & inhibitors ; Cell Adhesion Molecules - metabolism ; Cumulus Cells - metabolism ; Dioxoles - pharmacology ; Epidermal Growth Factor - metabolism ; Female ; Follicle Stimulating Hormone - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation, Developmental - drug effects ; Glucuronosyltransferase - antagonists & inhibitors ; Glucuronosyltransferase - metabolism ; Hormone metabolism and regulation ; hyaluronan ; Hyaluronic Acid - biosynthesis ; Isoquinolines - pharmacology ; Mammalian female genital system ; Meiosis - drug effects ; Mice ; oocyte-cumulus complex ; Oocytes - enzymology ; Oocytes - physiology ; progesterone ; Progesterone - biosynthesis ; Pyridines - pharmacology ; Pyrroles - pharmacology ; Quinazolines - pharmacology ; Receptor, Epidermal Growth Factor - antagonists & inhibitors ; Receptor, Epidermal Growth Factor - metabolism ; Serum Amyloid P-Component - metabolism ; Signal Transduction - drug effects ; Smad2 Protein - antagonists & inhibitors ; Smad2 Protein - metabolism ; Smad3 Protein - antagonists & inhibitors ; Smad3 Protein - metabolism ; Swine ; Tyrphostins - pharmacology ; Vertebrates: reproduction</subject><ispartof>Molecular reproduction and development, 2011-06, Vol.78 (6), p.391-402</ispartof><rights>Copyright © 2011 Wiley‐Liss, Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4582-26e743fc46114fa5594f0ab234dd9525cd54593e124436270a8ee9103ab6c5233</citedby><cites>FETCH-LOGICAL-c4582-26e743fc46114fa5594f0ab234dd9525cd54593e124436270a8ee9103ab6c5233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmrd.21312$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmrd.21312$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24280727$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21520325$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nagyova, Eva</creatorcontrib><creatorcontrib>Camaioni, Antonella</creatorcontrib><creatorcontrib>Scsukova, Sona</creatorcontrib><creatorcontrib>Mlynarcikova, Alzbeta</creatorcontrib><creatorcontrib>Prochazka, Radek</creatorcontrib><creatorcontrib>Nemcova, Lucie</creatorcontrib><creatorcontrib>Salustri, Antonietta</creatorcontrib><title>Activation of cumulus cell SMAD2/3 and epidermal growth factor receptor pathways are involved in porcine oocyte-cumulus cell expansion and steroidogenesis</title><title>Molecular reproduction and development</title><addtitle>Mol. Reprod. Dev</addtitle><description>Several lines of evidence suggest that in mice the activation of SMAD2/3 signaling by oocyte secreted factors, together with epidermal growth factor receptor (EGFR) activation, is essential to induce cumulus expansion. Here we show that inhibition of EGFR kinase in follicle stimulating hormone (FSH)‐stimulated porcine oocyte–cumulus cell complex (OCCs) strongly decreases hyaluronan (HA) synthesis and its retention in the matrix, as well as progesterone synthesis. Although porcine cumulus cells undergo expansion independently of oocytes, we use biochemical and gene expression analyses to show that they do require activation of SMAD2/3 for optimal stimulation of HA synthesis and proteins involved in the organization of this polymer in the expanded matrix. Furthermore, FSH‐induced progesterone synthesis by porcine cumulus cells was increased by blocking SMAD2/3 activation. In conclusion, these results support the hypothesis that an FSH–EGF autocrine loop is active in porcine OCCs, and provide the first evidence that the SMAD2/3 signaling pathway is induced by paracrine/autocrine factors in porcine cumulus cells and is involved in the control of both cumulus expansion and steroidogenesis. Mol. Reprod. Dev. 78:391–402, 2011. © 2011 Wiley‐Liss, Inc.</description><subject>Animals</subject><subject>Benzamides - pharmacology</subject><subject>Biological and medical sciences</subject><subject>C-Reactive Protein - metabolism</subject><subject>Cell Adhesion Molecules - antagonists & inhibitors</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cumulus Cells - metabolism</subject><subject>Dioxoles - pharmacology</subject><subject>Epidermal Growth Factor - metabolism</subject><subject>Female</subject><subject>Follicle Stimulating Hormone - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>Glucuronosyltransferase - antagonists & inhibitors</subject><subject>Glucuronosyltransferase - metabolism</subject><subject>Hormone metabolism and regulation</subject><subject>hyaluronan</subject><subject>Hyaluronic Acid - biosynthesis</subject><subject>Isoquinolines - pharmacology</subject><subject>Mammalian female genital system</subject><subject>Meiosis - drug effects</subject><subject>Mice</subject><subject>oocyte-cumulus complex</subject><subject>Oocytes - enzymology</subject><subject>Oocytes - physiology</subject><subject>progesterone</subject><subject>Progesterone - biosynthesis</subject><subject>Pyridines - pharmacology</subject><subject>Pyrroles - pharmacology</subject><subject>Quinazolines - pharmacology</subject><subject>Receptor, Epidermal Growth Factor - antagonists & inhibitors</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Serum Amyloid P-Component - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Smad2 Protein - antagonists & inhibitors</subject><subject>Smad2 Protein - metabolism</subject><subject>Smad3 Protein - antagonists & inhibitors</subject><subject>Smad3 Protein - metabolism</subject><subject>Swine</subject><subject>Tyrphostins - pharmacology</subject><subject>Vertebrates: reproduction</subject><issn>1040-452X</issn><issn>1098-2795</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctu1DAUhi0EoqWw4AWQNwh1kY6vuSxHLZ0itUWCIqpurDPOSWtI4tROZjqvwtOSMNMiFqz8L75zPuv8hLzl7IgzJmZNKI8El1w8I_ucFXkiskI_n7JiidLieo-8ivEHY6wocvaS7AmuBZNC75Nfc9u7FfTOt9RX1A7NUA-RWqxr-vVifiJmkkJbUuxciaGBmt4Gv-7vaAW294EGtNhNoYP-bg2bSCEgde3K1yssx0A7H6xrkXpvNz0m_xjwoYM2Tu7JEXsM3pX-FluMLr4mLyqoI77ZvQfk2-nHq-Oz5Pzz4tPx_DyxSuciESlmSlZWpZyrCrQuVMVgKaQqy0ILbUutdCGRC6VkKjIGOWLBmYRlarWQ8oB82O7tgr8fMPamcXH6HrToh2jyTEqeSqFG8nBL2uBjDFiZLrgGwsZwZqYmzNiE-dPEyL7bbR2WDZZP5OPpR-D9DoBooa4CtNbFv5wSOctENnKzLbd2NW7-bzQXX04e1cl2wo0XfXiagPDTpJnMtPl-uTBX6dn1zeLm0jD5G3_SsKQ</recordid><startdate>201106</startdate><enddate>201106</enddate><creator>Nagyova, Eva</creator><creator>Camaioni, Antonella</creator><creator>Scsukova, Sona</creator><creator>Mlynarcikova, Alzbeta</creator><creator>Prochazka, Radek</creator><creator>Nemcova, Lucie</creator><creator>Salustri, Antonietta</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><scope>BSCLL</scope><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>201106</creationdate><title>Activation of cumulus cell SMAD2/3 and epidermal growth factor receptor pathways are involved in porcine oocyte-cumulus cell expansion and steroidogenesis</title><author>Nagyova, Eva ; Camaioni, Antonella ; Scsukova, Sona ; Mlynarcikova, Alzbeta ; Prochazka, Radek ; Nemcova, Lucie ; Salustri, Antonietta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4582-26e743fc46114fa5594f0ab234dd9525cd54593e124436270a8ee9103ab6c5233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Benzamides - pharmacology</topic><topic>Biological and medical sciences</topic><topic>C-Reactive Protein - metabolism</topic><topic>Cell Adhesion Molecules - antagonists & inhibitors</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Cumulus Cells - metabolism</topic><topic>Dioxoles - pharmacology</topic><topic>Epidermal Growth Factor - metabolism</topic><topic>Female</topic><topic>Follicle Stimulating Hormone - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>Glucuronosyltransferase - antagonists & inhibitors</topic><topic>Glucuronosyltransferase - metabolism</topic><topic>Hormone metabolism and regulation</topic><topic>hyaluronan</topic><topic>Hyaluronic Acid - biosynthesis</topic><topic>Isoquinolines - pharmacology</topic><topic>Mammalian female genital system</topic><topic>Meiosis - drug effects</topic><topic>Mice</topic><topic>oocyte-cumulus complex</topic><topic>Oocytes - enzymology</topic><topic>Oocytes - physiology</topic><topic>progesterone</topic><topic>Progesterone - biosynthesis</topic><topic>Pyridines - pharmacology</topic><topic>Pyrroles - pharmacology</topic><topic>Quinazolines - pharmacology</topic><topic>Receptor, Epidermal Growth Factor - antagonists & inhibitors</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>Serum Amyloid P-Component - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Smad2 Protein - antagonists & inhibitors</topic><topic>Smad2 Protein - metabolism</topic><topic>Smad3 Protein - antagonists & inhibitors</topic><topic>Smad3 Protein - metabolism</topic><topic>Swine</topic><topic>Tyrphostins - pharmacology</topic><topic>Vertebrates: reproduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nagyova, Eva</creatorcontrib><creatorcontrib>Camaioni, Antonella</creatorcontrib><creatorcontrib>Scsukova, Sona</creatorcontrib><creatorcontrib>Mlynarcikova, Alzbeta</creatorcontrib><creatorcontrib>Prochazka, Radek</creatorcontrib><creatorcontrib>Nemcova, Lucie</creatorcontrib><creatorcontrib>Salustri, Antonietta</creatorcontrib><collection>Istex</collection><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>Molecular reproduction and development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nagyova, Eva</au><au>Camaioni, Antonella</au><au>Scsukova, Sona</au><au>Mlynarcikova, Alzbeta</au><au>Prochazka, Radek</au><au>Nemcova, Lucie</au><au>Salustri, Antonietta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of cumulus cell SMAD2/3 and epidermal growth factor receptor pathways are involved in porcine oocyte-cumulus cell expansion and steroidogenesis</atitle><jtitle>Molecular reproduction and development</jtitle><addtitle>Mol. Reprod. Dev</addtitle><date>2011-06</date><risdate>2011</risdate><volume>78</volume><issue>6</issue><spage>391</spage><epage>402</epage><pages>391-402</pages><issn>1040-452X</issn><eissn>1098-2795</eissn><coden>MREDEE</coden><abstract>Several lines of evidence suggest that in mice the activation of SMAD2/3 signaling by oocyte secreted factors, together with epidermal growth factor receptor (EGFR) activation, is essential to induce cumulus expansion. Here we show that inhibition of EGFR kinase in follicle stimulating hormone (FSH)‐stimulated porcine oocyte–cumulus cell complex (OCCs) strongly decreases hyaluronan (HA) synthesis and its retention in the matrix, as well as progesterone synthesis. Although porcine cumulus cells undergo expansion independently of oocytes, we use biochemical and gene expression analyses to show that they do require activation of SMAD2/3 for optimal stimulation of HA synthesis and proteins involved in the organization of this polymer in the expanded matrix. Furthermore, FSH‐induced progesterone synthesis by porcine cumulus cells was increased by blocking SMAD2/3 activation. In conclusion, these results support the hypothesis that an FSH–EGF autocrine loop is active in porcine OCCs, and provide the first evidence that the SMAD2/3 signaling pathway is induced by paracrine/autocrine factors in porcine cumulus cells and is involved in the control of both cumulus expansion and steroidogenesis. Mol. Reprod. Dev. 78:391–402, 2011. © 2011 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21520325</pmid><doi>10.1002/mrd.21312</doi><tpages>12</tpages></addata></record> |
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| ispartof | Molecular reproduction and development, 2011-06, Vol.78 (6), p.391-402 |
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| subjects | Animals Benzamides - pharmacology Biological and medical sciences C-Reactive Protein - metabolism Cell Adhesion Molecules - antagonists & inhibitors Cell Adhesion Molecules - metabolism Cumulus Cells - metabolism Dioxoles - pharmacology Epidermal Growth Factor - metabolism Female Follicle Stimulating Hormone - metabolism Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Developmental - drug effects Glucuronosyltransferase - antagonists & inhibitors Glucuronosyltransferase - metabolism Hormone metabolism and regulation hyaluronan Hyaluronic Acid - biosynthesis Isoquinolines - pharmacology Mammalian female genital system Meiosis - drug effects Mice oocyte-cumulus complex Oocytes - enzymology Oocytes - physiology progesterone Progesterone - biosynthesis Pyridines - pharmacology Pyrroles - pharmacology Quinazolines - pharmacology Receptor, Epidermal Growth Factor - antagonists & inhibitors Receptor, Epidermal Growth Factor - metabolism Serum Amyloid P-Component - metabolism Signal Transduction - drug effects Smad2 Protein - antagonists & inhibitors Smad2 Protein - metabolism Smad3 Protein - antagonists & inhibitors Smad3 Protein - metabolism Swine Tyrphostins - pharmacology Vertebrates: reproduction |
| title | Activation of cumulus cell SMAD2/3 and epidermal growth factor receptor pathways are involved in porcine oocyte-cumulus cell expansion and steroidogenesis |
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