Effects of metformin and ganirelix on subcutaneous endometriosis in a mouse model of autophagy-related cell death/Otofaji ile iliskili hucrelerde subkutan endometriozis fare modelinde metformin ve genireliksin etkisi
Objective: This study aimed to investigate the efficacy of metformin and ganirelix on subcutaneous endometriotic tissues created in an experimental mouse model. Materials and Methods: Five groups were formed with eight animals in each group. One of the groups was set as the control group. Endometrio...
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Veröffentlicht in: | Turkish journal of obstetrics and gynecology 2023-09, Vol.20 (3), p.219 |
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creator | Unal, Gamze Sonmez Albak, Yasemin Yurtcu, Nazan Yildiz, Caglar Cetin, Meral Dastan, Sevgi Durna Gumus, Erkan Cetin, Ali |
description | Objective: This study aimed to investigate the efficacy of metformin and ganirelix on subcutaneous endometriotic tissues created in an experimental mouse model. Materials and Methods: Five groups were formed with eight animals in each group. One of the groups was set as the control group. Endometriotic lesions were created by transplanting 40 mouse autologous endomyometrial tissues into the mouse subcutaneous tissue to a highly vascular surface. Gene expression analyzes of tissues were performed as HIF-1a, ATG5, ATG12, Beclin2, Beclin1, LC3BII, CateninB, GSK3b, TCF, WNT2, WNT7a, and WNT10a gene analyzes. Drug effects were examined by histological examination. HIF1a and WNT2 protein expressions were examined immunohistochemically. Gene expression coefficients of control, metformin day 1 (Met1g), metformin day 7 (Met7g), ganirelix day 1 (Gnx1g), and ganirelix day 7 (Gnx7g) groups are shown in tables. Data are presented as mean and standard error. Results: Beclin2 gene expression coefficients of metformin 1st day, metformin 7th day, ganirelix 1st day, and general 7th day groups were found to have significantly decreased compared with the control group coefficient. Beclin1 gene expression coefficients of metformin 1st day, metformin 7th day, ganirelix 1st day, and genirelix 7th day groups were found to have significantly decreased compared with the control group coefficient. LC3BII gene expression coefficients of metformin 1st day and metformin 7th day groups were found to have significantly decreased compared with LC3BII gene expression coefficients of control, genirelix 1st day, and genirelix 7th day groups. These findings were supported by histological and immunohistochemical staining. Conclusion: These genes are actively involved in the autophagy pathway, and we think that the use of metformin in endometriosis might create an autophagy-based suppression mechanism. Keywords: Endometriosis, ganirelix, metformin, subcutaneous endometriosis, mouse model Amac: Bu calismanin amaci, deneysel bir fare modelinde olusturulan deri alti endometriotik dokular uzerindeki metformin ve genireliksin etkinligini arastirmaktir. Gerec ve Yontemler: Her grupta 8 hayvan olacak sekilde 5 grup olusturuldu. Gruplardan biri kontrol grubu olarak belirlendi. Endometriotik lezyonlar, 40 adet farenin otolog endomyometrial dokusunun fare deri alti dokusuna vaskuler bir yuzeye nakledilmesiyle olusturuldu. Dokularin gen ekspresyon analizleri HIF1a, ATG5, ATG12, Beclin2, Beclin1, LC3BII, C |
doi_str_mv | 10.4274/tjod.galenos.2023.85616 |
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Materials and Methods: Five groups were formed with eight animals in each group. One of the groups was set as the control group. Endometriotic lesions were created by transplanting 40 mouse autologous endomyometrial tissues into the mouse subcutaneous tissue to a highly vascular surface. Gene expression analyzes of tissues were performed as HIF-1a, ATG5, ATG12, Beclin2, Beclin1, LC3BII, CateninB, GSK3b, TCF, WNT2, WNT7a, and WNT10a gene analyzes. Drug effects were examined by histological examination. HIF1a and WNT2 protein expressions were examined immunohistochemically. Gene expression coefficients of control, metformin day 1 (Met1g), metformin day 7 (Met7g), ganirelix day 1 (Gnx1g), and ganirelix day 7 (Gnx7g) groups are shown in tables. Data are presented as mean and standard error. Results: Beclin2 gene expression coefficients of metformin 1st day, metformin 7th day, ganirelix 1st day, and general 7th day groups were found to have significantly decreased compared with the control group coefficient. Beclin1 gene expression coefficients of metformin 1st day, metformin 7th day, ganirelix 1st day, and genirelix 7th day groups were found to have significantly decreased compared with the control group coefficient. LC3BII gene expression coefficients of metformin 1st day and metformin 7th day groups were found to have significantly decreased compared with LC3BII gene expression coefficients of control, genirelix 1st day, and genirelix 7th day groups. These findings were supported by histological and immunohistochemical staining. Conclusion: These genes are actively involved in the autophagy pathway, and we think that the use of metformin in endometriosis might create an autophagy-based suppression mechanism. Keywords: Endometriosis, ganirelix, metformin, subcutaneous endometriosis, mouse model Amac: Bu calismanin amaci, deneysel bir fare modelinde olusturulan deri alti endometriotik dokular uzerindeki metformin ve genireliksin etkinligini arastirmaktir. Gerec ve Yontemler: Her grupta 8 hayvan olacak sekilde 5 grup olusturuldu. Gruplardan biri kontrol grubu olarak belirlendi. Endometriotik lezyonlar, 40 adet farenin otolog endomyometrial dokusunun fare deri alti dokusuna vaskuler bir yuzeye nakledilmesiyle olusturuldu. Dokularin gen ekspresyon analizleri HIF1a, ATG5, ATG12, Beclin2, Beclin1, LC3BII, CateninB, GSK3b, TCF, WNT2, WNT7a, WNT10a gen analizleri olarak yapildi. Histolojik inceleme ile ilac etkileri incelendi. Immunohistokimyasal olarak HIF1a and WNT2 protein ifadelenmeleri incelendi. Bulgular: Metformin 1. gun, metformin 7. gun, genireliks 1. gun, genireliks 7. gun gruplarinin Beclin2 gen ifadelenme katsayilari kontrol grubu katsayisi ile karsilastirildiginda anlamli olarak azalmis bulundu. Metformin 1. gun, metformin 7. gun, genireliks 1. gun, genireliks 7. gun gruplarinin Beclin1 gen ifadelenme katsayilari kontrol grubu katsayisi ile karsilastirildiginda anlamli olarak azalmis bulundu. Metformin 1. gun, metformin 7. gun gruplarinin LC3BII gen ifadelenme katsayilari kontrol, genireliks 1. gun ve genireliks 7. gun gruplarinin LC3BII gen ifadelenme katsayilari ile karsilastirildiginda anlamli olarak azalmis bulundu. Histolojik ve immunohistokimyasal boyamalar ile bu bulgular desteklendi. Sonuc: Arastirma kapsamina alinan genler aktif olarak otofaji yolunda yer almaktadir, arastirma bulgulari endometrioziste etkin kabul edilen genireliks ile ayni arastirma duzeneginde incelenen metforminin otofajiye dayali bir baskilama mekanizmasi olusturarak endometriotik odaklari baskiladigini desteklemektedir. Anahtar Kelimeler: Endometriozis, genirelix, metformin, subkutan endometriozis, fare modeli</description><identifier>ISSN: 2149-9322</identifier><identifier>DOI: 10.4274/tjod.galenos.2023.85616</identifier><language>eng</language><publisher>Galenos Yayinevi Tic. Ltd</publisher><subject>Analysis ; Autophagy (Cytology) ; Development and progression ; Dosage and administration ; Drug therapy ; Endometriosis ; Fertility drugs ; Ganirelix ; Gene expression ; Genes ; Genetic aspects ; Health aspects ; Hypoglycemic agents ; Immunohistochemistry ; Metformin ; Mice ; Patient outcomes ; Scientific equipment and supplies industry</subject><ispartof>Turkish journal of obstetrics and gynecology, 2023-09, Vol.20 (3), p.219</ispartof><rights>COPYRIGHT 2023 Galenos Yayinevi Tic. Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932</link.rule.ids></links><search><creatorcontrib>Unal, Gamze Sonmez</creatorcontrib><creatorcontrib>Albak, Yasemin</creatorcontrib><creatorcontrib>Yurtcu, Nazan</creatorcontrib><creatorcontrib>Yildiz, Caglar</creatorcontrib><creatorcontrib>Cetin, Meral</creatorcontrib><creatorcontrib>Dastan, Sevgi Durna</creatorcontrib><creatorcontrib>Gumus, Erkan</creatorcontrib><creatorcontrib>Cetin, Ali</creatorcontrib><title>Effects of metformin and ganirelix on subcutaneous endometriosis in a mouse model of autophagy-related cell death/Otofaji ile iliskili hucrelerde subkutan endometriozis fare modelinde metformin ve genireliksin etkisi</title><title>Turkish journal of obstetrics and gynecology</title><description>Objective: This study aimed to investigate the efficacy of metformin and ganirelix on subcutaneous endometriotic tissues created in an experimental mouse model. Materials and Methods: Five groups were formed with eight animals in each group. One of the groups was set as the control group. Endometriotic lesions were created by transplanting 40 mouse autologous endomyometrial tissues into the mouse subcutaneous tissue to a highly vascular surface. Gene expression analyzes of tissues were performed as HIF-1a, ATG5, ATG12, Beclin2, Beclin1, LC3BII, CateninB, GSK3b, TCF, WNT2, WNT7a, and WNT10a gene analyzes. Drug effects were examined by histological examination. HIF1a and WNT2 protein expressions were examined immunohistochemically. Gene expression coefficients of control, metformin day 1 (Met1g), metformin day 7 (Met7g), ganirelix day 1 (Gnx1g), and ganirelix day 7 (Gnx7g) groups are shown in tables. Data are presented as mean and standard error. Results: Beclin2 gene expression coefficients of metformin 1st day, metformin 7th day, ganirelix 1st day, and general 7th day groups were found to have significantly decreased compared with the control group coefficient. Beclin1 gene expression coefficients of metformin 1st day, metformin 7th day, ganirelix 1st day, and genirelix 7th day groups were found to have significantly decreased compared with the control group coefficient. LC3BII gene expression coefficients of metformin 1st day and metformin 7th day groups were found to have significantly decreased compared with LC3BII gene expression coefficients of control, genirelix 1st day, and genirelix 7th day groups. These findings were supported by histological and immunohistochemical staining. Conclusion: These genes are actively involved in the autophagy pathway, and we think that the use of metformin in endometriosis might create an autophagy-based suppression mechanism. Keywords: Endometriosis, ganirelix, metformin, subcutaneous endometriosis, mouse model Amac: Bu calismanin amaci, deneysel bir fare modelinde olusturulan deri alti endometriotik dokular uzerindeki metformin ve genireliksin etkinligini arastirmaktir. Gerec ve Yontemler: Her grupta 8 hayvan olacak sekilde 5 grup olusturuldu. Gruplardan biri kontrol grubu olarak belirlendi. Endometriotik lezyonlar, 40 adet farenin otolog endomyometrial dokusunun fare deri alti dokusuna vaskuler bir yuzeye nakledilmesiyle olusturuldu. Dokularin gen ekspresyon analizleri HIF1a, ATG5, ATG12, Beclin2, Beclin1, LC3BII, CateninB, GSK3b, TCF, WNT2, WNT7a, WNT10a gen analizleri olarak yapildi. Histolojik inceleme ile ilac etkileri incelendi. Immunohistokimyasal olarak HIF1a and WNT2 protein ifadelenmeleri incelendi. Bulgular: Metformin 1. gun, metformin 7. gun, genireliks 1. gun, genireliks 7. gun gruplarinin Beclin2 gen ifadelenme katsayilari kontrol grubu katsayisi ile karsilastirildiginda anlamli olarak azalmis bulundu. Metformin 1. gun, metformin 7. gun, genireliks 1. gun, genireliks 7. gun gruplarinin Beclin1 gen ifadelenme katsayilari kontrol grubu katsayisi ile karsilastirildiginda anlamli olarak azalmis bulundu. Metformin 1. gun, metformin 7. gun gruplarinin LC3BII gen ifadelenme katsayilari kontrol, genireliks 1. gun ve genireliks 7. gun gruplarinin LC3BII gen ifadelenme katsayilari ile karsilastirildiginda anlamli olarak azalmis bulundu. Histolojik ve immunohistokimyasal boyamalar ile bu bulgular desteklendi. Sonuc: Arastirma kapsamina alinan genler aktif olarak otofaji yolunda yer almaktadir, arastirma bulgulari endometrioziste etkin kabul edilen genireliks ile ayni arastirma duzeneginde incelenen metforminin otofajiye dayali bir baskilama mekanizmasi olusturarak endometriotik odaklari baskiladigini desteklemektedir. Anahtar Kelimeler: Endometriozis, genirelix, metformin, subkutan endometriozis, fare modeli</description><subject>Analysis</subject><subject>Autophagy (Cytology)</subject><subject>Development and progression</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Endometriosis</subject><subject>Fertility drugs</subject><subject>Ganirelix</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Hypoglycemic agents</subject><subject>Immunohistochemistry</subject><subject>Metformin</subject><subject>Mice</subject><subject>Patient outcomes</subject><subject>Scientific equipment and supplies industry</subject><issn>2149-9322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNptkM9KxDAQxntQUNRnMOC53SRtk_Yo4j8Q9rL3ZUwm3WzbRJpU1Cf1cUzZBT3IMBMy_Ob7hsmya0aListqFfdeFx0M6HwoOOVl0dSCiZPsnLOqzduS87PsKoQ9pZQ1UraMn2ff98agioF4Q0aMxk-jdQScJh04O-FgP4h3JMyvao7g0M-BoNM-sZP1wQay4GRMfUxV47AowRz92w66zzwpQERNFA4D0Qhxt1pHb2BviR0wpQ19KmQ3q4TipHHx6hevPz5fycfAdHSwLlG_y74j6fCwax_SH2Nvg73MTg0MAa-O70W2ebjf3D3lL-vH57vbl7wTUuSiAl1zAZo1WDFJVQVtqVspJaetMtAA03XFBG8w9Tk1hpYNq7mkoqXQNuVFdnOQXQ6_tc74OIEabVDbWynqklayFIkq_qFSaByt8g5NOsbfgR_CVZZR</recordid><startdate>20230901</startdate><enddate>20230901</enddate><creator>Unal, Gamze Sonmez</creator><creator>Albak, Yasemin</creator><creator>Yurtcu, Nazan</creator><creator>Yildiz, Caglar</creator><creator>Cetin, Meral</creator><creator>Dastan, Sevgi Durna</creator><creator>Gumus, Erkan</creator><creator>Cetin, Ali</creator><general>Galenos Yayinevi Tic. Ltd</general><scope/></search><sort><creationdate>20230901</creationdate><title>Effects of metformin and ganirelix on subcutaneous endometriosis in a mouse model of autophagy-related cell death/Otofaji ile iliskili hucrelerde subkutan endometriozis fare modelinde metformin ve genireliksin etkisi</title><author>Unal, Gamze Sonmez ; Albak, Yasemin ; Yurtcu, Nazan ; Yildiz, Caglar ; Cetin, Meral ; Dastan, Sevgi Durna ; Gumus, Erkan ; Cetin, Ali</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g676-64ad526ad18e4170c4a93d9777209cfa8a1d541628e93d20ff03815270690a983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analysis</topic><topic>Autophagy (Cytology)</topic><topic>Development and progression</topic><topic>Dosage and administration</topic><topic>Drug therapy</topic><topic>Endometriosis</topic><topic>Fertility drugs</topic><topic>Ganirelix</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Hypoglycemic agents</topic><topic>Immunohistochemistry</topic><topic>Metformin</topic><topic>Mice</topic><topic>Patient outcomes</topic><topic>Scientific equipment and supplies industry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Unal, Gamze Sonmez</creatorcontrib><creatorcontrib>Albak, Yasemin</creatorcontrib><creatorcontrib>Yurtcu, Nazan</creatorcontrib><creatorcontrib>Yildiz, Caglar</creatorcontrib><creatorcontrib>Cetin, Meral</creatorcontrib><creatorcontrib>Dastan, Sevgi Durna</creatorcontrib><creatorcontrib>Gumus, Erkan</creatorcontrib><creatorcontrib>Cetin, Ali</creatorcontrib><jtitle>Turkish journal of obstetrics and gynecology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Unal, Gamze Sonmez</au><au>Albak, Yasemin</au><au>Yurtcu, Nazan</au><au>Yildiz, Caglar</au><au>Cetin, Meral</au><au>Dastan, Sevgi Durna</au><au>Gumus, Erkan</au><au>Cetin, Ali</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of metformin and ganirelix on subcutaneous endometriosis in a mouse model of autophagy-related cell death/Otofaji ile iliskili hucrelerde subkutan endometriozis fare modelinde metformin ve genireliksin etkisi</atitle><jtitle>Turkish journal of obstetrics and gynecology</jtitle><date>2023-09-01</date><risdate>2023</risdate><volume>20</volume><issue>3</issue><spage>219</spage><pages>219-</pages><issn>2149-9322</issn><abstract>Objective: This study aimed to investigate the efficacy of metformin and ganirelix on subcutaneous endometriotic tissues created in an experimental mouse model. Materials and Methods: Five groups were formed with eight animals in each group. One of the groups was set as the control group. Endometriotic lesions were created by transplanting 40 mouse autologous endomyometrial tissues into the mouse subcutaneous tissue to a highly vascular surface. Gene expression analyzes of tissues were performed as HIF-1a, ATG5, ATG12, Beclin2, Beclin1, LC3BII, CateninB, GSK3b, TCF, WNT2, WNT7a, and WNT10a gene analyzes. Drug effects were examined by histological examination. HIF1a and WNT2 protein expressions were examined immunohistochemically. Gene expression coefficients of control, metformin day 1 (Met1g), metformin day 7 (Met7g), ganirelix day 1 (Gnx1g), and ganirelix day 7 (Gnx7g) groups are shown in tables. Data are presented as mean and standard error. Results: Beclin2 gene expression coefficients of metformin 1st day, metformin 7th day, ganirelix 1st day, and general 7th day groups were found to have significantly decreased compared with the control group coefficient. Beclin1 gene expression coefficients of metformin 1st day, metformin 7th day, ganirelix 1st day, and genirelix 7th day groups were found to have significantly decreased compared with the control group coefficient. LC3BII gene expression coefficients of metformin 1st day and metformin 7th day groups were found to have significantly decreased compared with LC3BII gene expression coefficients of control, genirelix 1st day, and genirelix 7th day groups. These findings were supported by histological and immunohistochemical staining. Conclusion: These genes are actively involved in the autophagy pathway, and we think that the use of metformin in endometriosis might create an autophagy-based suppression mechanism. Keywords: Endometriosis, ganirelix, metformin, subcutaneous endometriosis, mouse model Amac: Bu calismanin amaci, deneysel bir fare modelinde olusturulan deri alti endometriotik dokular uzerindeki metformin ve genireliksin etkinligini arastirmaktir. Gerec ve Yontemler: Her grupta 8 hayvan olacak sekilde 5 grup olusturuldu. Gruplardan biri kontrol grubu olarak belirlendi. Endometriotik lezyonlar, 40 adet farenin otolog endomyometrial dokusunun fare deri alti dokusuna vaskuler bir yuzeye nakledilmesiyle olusturuldu. Dokularin gen ekspresyon analizleri HIF1a, ATG5, ATG12, Beclin2, Beclin1, LC3BII, CateninB, GSK3b, TCF, WNT2, WNT7a, WNT10a gen analizleri olarak yapildi. Histolojik inceleme ile ilac etkileri incelendi. Immunohistokimyasal olarak HIF1a and WNT2 protein ifadelenmeleri incelendi. Bulgular: Metformin 1. gun, metformin 7. gun, genireliks 1. gun, genireliks 7. gun gruplarinin Beclin2 gen ifadelenme katsayilari kontrol grubu katsayisi ile karsilastirildiginda anlamli olarak azalmis bulundu. Metformin 1. gun, metformin 7. gun, genireliks 1. gun, genireliks 7. gun gruplarinin Beclin1 gen ifadelenme katsayilari kontrol grubu katsayisi ile karsilastirildiginda anlamli olarak azalmis bulundu. Metformin 1. gun, metformin 7. gun gruplarinin LC3BII gen ifadelenme katsayilari kontrol, genireliks 1. gun ve genireliks 7. gun gruplarinin LC3BII gen ifadelenme katsayilari ile karsilastirildiginda anlamli olarak azalmis bulundu. Histolojik ve immunohistokimyasal boyamalar ile bu bulgular desteklendi. Sonuc: Arastirma kapsamina alinan genler aktif olarak otofaji yolunda yer almaktadir, arastirma bulgulari endometrioziste etkin kabul edilen genireliks ile ayni arastirma duzeneginde incelenen metforminin otofajiye dayali bir baskilama mekanizmasi olusturarak endometriotik odaklari baskiladigini desteklemektedir. Anahtar Kelimeler: Endometriozis, genirelix, metformin, subkutan endometriozis, fare modeli</abstract><pub>Galenos Yayinevi Tic. Ltd</pub><doi>10.4274/tjod.galenos.2023.85616</doi></addata></record> |
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subjects | Analysis Autophagy (Cytology) Development and progression Dosage and administration Drug therapy Endometriosis Fertility drugs Ganirelix Gene expression Genes Genetic aspects Health aspects Hypoglycemic agents Immunohistochemistry Metformin Mice Patient outcomes Scientific equipment and supplies industry |
title | Effects of metformin and ganirelix on subcutaneous endometriosis in a mouse model of autophagy-related cell death/Otofaji ile iliskili hucrelerde subkutan endometriozis fare modelinde metformin ve genireliksin etkisi |
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