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Intra-cervical application of Misoprostol at estrus alters the content of cervical hyaluronan and the mRNA expression of follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR) and cyclooxygenase-2 in the ewe
The complex anatomy the of ovine cervix limits the success of transcervical artificial insemination in sheep, but Misoprostol (a PGE1 analogue) relaxes the cervix and facilitates transcervical artificial insemination. However, the mechanism by which Misoprostol causes cervical relaxation is not know...
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Published in: | Theriogenology 2010-06, Vol.73 (9), p.1257-1266 |
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description | The complex anatomy the of ovine cervix limits the success of transcervical artificial insemination in sheep, but Misoprostol (a PGE1 analogue) relaxes the cervix and facilitates transcervical artificial insemination. However, the mechanism by which Misoprostol causes cervical relaxation is not known. This study examined if intra-cervical Misoprostol altered the hyaluronan content and the mRNA expression of COX-2, LHR, or FSHR in the cervix of the estrus ewe. Estrus was synchronized in cyclic ewes with progestagen pessaries and 48h after sponge removal ewes were treated intra-cervically with 0 (controls), 200, or 400μg Misoprostol. Hyaluronan content was determined by ELISA and mRNA expression of LHR, FSHR, and COX-2 was analyzed by in situ hybridization using digoxigenin-11-uridine-5′-triphosphate labeled riboprobes. The hyaluronan content of the cervix was significantly higher in sheep that received 200 (P |
doi_str_mv | 10.1016/j.theriogenology.2009.12.005 |
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However, the mechanism by which Misoprostol causes cervical relaxation is not known. This study examined if intra-cervical Misoprostol altered the hyaluronan content and the mRNA expression of COX-2, LHR, or FSHR in the cervix of the estrus ewe. Estrus was synchronized in cyclic ewes with progestagen pessaries and 48h after sponge removal ewes were treated intra-cervically with 0 (controls), 200, or 400μg Misoprostol. Hyaluronan content was determined by ELISA and mRNA expression of LHR, FSHR, and COX-2 was analyzed by in situ hybridization using digoxigenin-11-uridine-5′-triphosphate labeled riboprobes. The hyaluronan content of the cervix was significantly higher in sheep that received 200 (P<0.05) or 400 (P<0.05) μg Misoprostol compared to controls. Moreover, it was significantly (P<0.05) higher in the vaginal region compared to mid and uterine regions. Misoprostol increased (P<0.05) the mRNA expression of LHR and COX-2 but not FSHR. The expression for all three genes was highest in the vaginal region and lowest in uterine region. The luminal epithelium and circular smooth muscle layers had higher (P<0.05) expression for LHR, FSHR, and COX-2 mRNAs, and the sub-epithelial stroma had the lowest (P<0.05). We propose that the intra-cervical application of Misoprostol induces the mRNA expression of LHR, FSHR, and COX-2 through a positive feedback loop. The data suggest that softening of the cervix by Misoprostol is caused by an increase in the hyaluronan content of the cervix.]]></description><identifier>ISSN: 0093-691X</identifier><identifier>EISSN: 1879-3231</identifier><identifier>DOI: 10.1016/j.theriogenology.2009.12.005</identifier><identifier>PMID: 20171717</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; artificial insemination ; biochemical mechanisms ; biosynthesis ; Cervix ; Cervix Uteri - chemistry ; Cervix Uteri - drug effects ; controlled internal drug release devices ; COX-2 ; Cyclooxygenase 1 - genetics ; Estrus ; estrus synchronization ; ewes ; Feedback, Physiological ; Female ; follicle-stimulating hormone ; Gene Expression ; Gonadotrophin receptors ; hormonal regulation ; hormone receptors ; Hyaluronan ; hyaluronic acid ; Hyaluronic Acid - analysis ; In Situ Hybridization ; luteinizing hormone ; messenger RNA ; Misoprostol ; Misoprostol - administration & dosage ; physiological response ; prostaglandin synthase ; Receptors, FSH - genetics ; Receptors, Gonadotropin - genetics ; Receptors, LH - genetics ; RNA, Messenger - analysis ; Sheep - metabolism ; synthetic prostaglandins ; vagina</subject><ispartof>Theriogenology, 2010-06, Vol.73 (9), p.1257-1266</ispartof><rights>2010</rights><rights>2010. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-a312b9bae88a2bfcd89ade8c70c9b1fc37643c7350ddb373a9dfef40161e4d13</citedby><cites>FETCH-LOGICAL-c409t-a312b9bae88a2bfcd89ade8c70c9b1fc37643c7350ddb373a9dfef40161e4d13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20171717$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leethongdee, S.</creatorcontrib><creatorcontrib>Kershaw-Young, C.M.</creatorcontrib><creatorcontrib>Scaramuzzi, R.J.</creatorcontrib><creatorcontrib>Khalid, M.</creatorcontrib><title>Intra-cervical application of Misoprostol at estrus alters the content of cervical hyaluronan and the mRNA expression of follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR) and cyclooxygenase-2 in the ewe</title><title>Theriogenology</title><addtitle>Theriogenology</addtitle><description><![CDATA[The complex anatomy the of ovine cervix limits the success of transcervical artificial insemination in sheep, but Misoprostol (a PGE1 analogue) relaxes the cervix and facilitates transcervical artificial insemination. However, the mechanism by which Misoprostol causes cervical relaxation is not known. This study examined if intra-cervical Misoprostol altered the hyaluronan content and the mRNA expression of COX-2, LHR, or FSHR in the cervix of the estrus ewe. Estrus was synchronized in cyclic ewes with progestagen pessaries and 48h after sponge removal ewes were treated intra-cervically with 0 (controls), 200, or 400μg Misoprostol. Hyaluronan content was determined by ELISA and mRNA expression of LHR, FSHR, and COX-2 was analyzed by in situ hybridization using digoxigenin-11-uridine-5′-triphosphate labeled riboprobes. The hyaluronan content of the cervix was significantly higher in sheep that received 200 (P<0.05) or 400 (P<0.05) μg Misoprostol compared to controls. Moreover, it was significantly (P<0.05) higher in the vaginal region compared to mid and uterine regions. Misoprostol increased (P<0.05) the mRNA expression of LHR and COX-2 but not FSHR. The expression for all three genes was highest in the vaginal region and lowest in uterine region. The luminal epithelium and circular smooth muscle layers had higher (P<0.05) expression for LHR, FSHR, and COX-2 mRNAs, and the sub-epithelial stroma had the lowest (P<0.05). We propose that the intra-cervical application of Misoprostol induces the mRNA expression of LHR, FSHR, and COX-2 through a positive feedback loop. The data suggest that softening of the cervix by Misoprostol is caused by an increase in the hyaluronan content of the cervix.]]></description><subject>Animals</subject><subject>artificial insemination</subject><subject>biochemical mechanisms</subject><subject>biosynthesis</subject><subject>Cervix</subject><subject>Cervix Uteri - chemistry</subject><subject>Cervix Uteri - drug effects</subject><subject>controlled internal drug release devices</subject><subject>COX-2</subject><subject>Cyclooxygenase 1 - genetics</subject><subject>Estrus</subject><subject>estrus synchronization</subject><subject>ewes</subject><subject>Feedback, Physiological</subject><subject>Female</subject><subject>follicle-stimulating hormone</subject><subject>Gene Expression</subject><subject>Gonadotrophin receptors</subject><subject>hormonal regulation</subject><subject>hormone receptors</subject><subject>Hyaluronan</subject><subject>hyaluronic acid</subject><subject>Hyaluronic Acid - analysis</subject><subject>In Situ Hybridization</subject><subject>luteinizing hormone</subject><subject>messenger RNA</subject><subject>Misoprostol</subject><subject>Misoprostol - administration & dosage</subject><subject>physiological response</subject><subject>prostaglandin synthase</subject><subject>Receptors, FSH - genetics</subject><subject>Receptors, Gonadotropin - genetics</subject><subject>Receptors, LH - genetics</subject><subject>RNA, Messenger - analysis</subject><subject>Sheep - metabolism</subject><subject>synthetic prostaglandins</subject><subject>vagina</subject><issn>0093-691X</issn><issn>1879-3231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNqNkV1rFDEUhoModq3-Bc2FoIKzJpPpfIA3pXRtYVVoK3gXMsmZ3SyZZEwytdN_7L8w-2FB8EJycQLnOec9vC9CrymZU0LLD5t5XIPXbgXWGbea5jkhzZzmc0JOHqEZrasmYzmjj9EsNVhWNvT7EXoWwoYQwsqSPkVHOaHV9s3Qr0sbvcgk-FsthcFiGEz6RO0sdh3-rIMbvAvRpVbEEKIfAxYmgg843YGlsxFs3LIPO9aTMKN3VlgsrNph_dWXUwx3g4cQDqs7Z5KSARyi7keTJO0Kr53vnQXsQcIQncdvF9cXV-_eYzNG0Fbf_xtaJmanJSdpnLubkjkiQJZjbXf68BOeoyedMAFeHOoxulmc35xdZMuvny7PTpeZLEgTM8Fo3jatgLoWedtJVTdCQS0rIpuWdpJVZcFkxU6IUi2rmGhUB12RkqFQKMqO0Zv92mTbjzEZxnsdJBgjLLgx8IqxpiQ0LxL5cU_KZHDw0PHB6174iVPCt1HzDf87ar6NmtOcp6jT-MuD0Nj2oB6G_2SbgFd7oBOOi5XXgX-7Tl1GaF2QmtWJWOwJSH7cavA8SA1WgtLJ28iV0_93y29kWNPJ</recordid><startdate>20100601</startdate><enddate>20100601</enddate><creator>Leethongdee, S.</creator><creator>Kershaw-Young, C.M.</creator><creator>Scaramuzzi, R.J.</creator><creator>Khalid, M.</creator><general>Elsevier Inc</general><general>[Oxford]: Butterworth-Heinemann; [New York]: Elsevier Science</general><scope>FBQ</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>20100601</creationdate><title>Intra-cervical application of Misoprostol at estrus alters the content of cervical hyaluronan and the mRNA expression of follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR) and cyclooxygenase-2 in the ewe</title><author>Leethongdee, S. ; Kershaw-Young, C.M. ; Scaramuzzi, R.J. ; Khalid, M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-a312b9bae88a2bfcd89ade8c70c9b1fc37643c7350ddb373a9dfef40161e4d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>artificial insemination</topic><topic>biochemical mechanisms</topic><topic>biosynthesis</topic><topic>Cervix</topic><topic>Cervix Uteri - chemistry</topic><topic>Cervix Uteri - drug effects</topic><topic>controlled internal drug release devices</topic><topic>COX-2</topic><topic>Cyclooxygenase 1 - genetics</topic><topic>Estrus</topic><topic>estrus synchronization</topic><topic>ewes</topic><topic>Feedback, Physiological</topic><topic>Female</topic><topic>follicle-stimulating hormone</topic><topic>Gene Expression</topic><topic>Gonadotrophin receptors</topic><topic>hormonal regulation</topic><topic>hormone receptors</topic><topic>Hyaluronan</topic><topic>hyaluronic acid</topic><topic>Hyaluronic Acid - analysis</topic><topic>In Situ Hybridization</topic><topic>luteinizing hormone</topic><topic>messenger RNA</topic><topic>Misoprostol</topic><topic>Misoprostol - administration & dosage</topic><topic>physiological response</topic><topic>prostaglandin synthase</topic><topic>Receptors, FSH - genetics</topic><topic>Receptors, Gonadotropin - genetics</topic><topic>Receptors, LH - genetics</topic><topic>RNA, Messenger - analysis</topic><topic>Sheep - metabolism</topic><topic>synthetic prostaglandins</topic><topic>vagina</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leethongdee, S.</creatorcontrib><creatorcontrib>Kershaw-Young, C.M.</creatorcontrib><creatorcontrib>Scaramuzzi, R.J.</creatorcontrib><creatorcontrib>Khalid, M.</creatorcontrib><collection>AGRIS</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>Theriogenology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leethongdee, S.</au><au>Kershaw-Young, C.M.</au><au>Scaramuzzi, R.J.</au><au>Khalid, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intra-cervical application of Misoprostol at estrus alters the content of cervical hyaluronan and the mRNA expression of follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR) and cyclooxygenase-2 in the ewe</atitle><jtitle>Theriogenology</jtitle><addtitle>Theriogenology</addtitle><date>2010-06-01</date><risdate>2010</risdate><volume>73</volume><issue>9</issue><spage>1257</spage><epage>1266</epage><pages>1257-1266</pages><issn>0093-691X</issn><eissn>1879-3231</eissn><notes>http://dx.doi.org/10.1016/j.theriogenology.2009.12.005</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract><![CDATA[The complex anatomy the of ovine cervix limits the success of transcervical artificial insemination in sheep, but Misoprostol (a PGE1 analogue) relaxes the cervix and facilitates transcervical artificial insemination. However, the mechanism by which Misoprostol causes cervical relaxation is not known. This study examined if intra-cervical Misoprostol altered the hyaluronan content and the mRNA expression of COX-2, LHR, or FSHR in the cervix of the estrus ewe. Estrus was synchronized in cyclic ewes with progestagen pessaries and 48h after sponge removal ewes were treated intra-cervically with 0 (controls), 200, or 400μg Misoprostol. Hyaluronan content was determined by ELISA and mRNA expression of LHR, FSHR, and COX-2 was analyzed by in situ hybridization using digoxigenin-11-uridine-5′-triphosphate labeled riboprobes. The hyaluronan content of the cervix was significantly higher in sheep that received 200 (P<0.05) or 400 (P<0.05) μg Misoprostol compared to controls. Moreover, it was significantly (P<0.05) higher in the vaginal region compared to mid and uterine regions. Misoprostol increased (P<0.05) the mRNA expression of LHR and COX-2 but not FSHR. The expression for all three genes was highest in the vaginal region and lowest in uterine region. The luminal epithelium and circular smooth muscle layers had higher (P<0.05) expression for LHR, FSHR, and COX-2 mRNAs, and the sub-epithelial stroma had the lowest (P<0.05). We propose that the intra-cervical application of Misoprostol induces the mRNA expression of LHR, FSHR, and COX-2 through a positive feedback loop. The data suggest that softening of the cervix by Misoprostol is caused by an increase in the hyaluronan content of the cervix.]]></abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20171717</pmid><doi>10.1016/j.theriogenology.2009.12.005</doi><tpages>10</tpages></addata></record> |
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subjects | Animals artificial insemination biochemical mechanisms biosynthesis Cervix Cervix Uteri - chemistry Cervix Uteri - drug effects controlled internal drug release devices COX-2 Cyclooxygenase 1 - genetics Estrus estrus synchronization ewes Feedback, Physiological Female follicle-stimulating hormone Gene Expression Gonadotrophin receptors hormonal regulation hormone receptors Hyaluronan hyaluronic acid Hyaluronic Acid - analysis In Situ Hybridization luteinizing hormone messenger RNA Misoprostol Misoprostol - administration & dosage physiological response prostaglandin synthase Receptors, FSH - genetics Receptors, Gonadotropin - genetics Receptors, LH - genetics RNA, Messenger - analysis Sheep - metabolism synthetic prostaglandins vagina |
title | Intra-cervical application of Misoprostol at estrus alters the content of cervical hyaluronan and the mRNA expression of follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR) and cyclooxygenase-2 in the ewe |
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