Direct effect of metformin on healthy ovarian cells

Autores
Velazquez, Candela; Di Pietro, Mariana; Pascuali, Natalia Marisa; Parborell, Maria Fernanda Agustina; Abramovich, Dalhia Nurit
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Metformin (MET) is an oral antihyperglycemic drug introduced in the treatment of polycystic ovary syndrome (PCOS) to manage hyperglycemia. PCOS is a common disorder that affects women in reproductive age. MET improves ovulation, pregnancy and live birth rates in patients with PCOS. The mechanism by which MET of these effects are not fully understood. MET primary mechanism of action is through the activation of the AMP-activated protein kinase (AMPK), which acts as an energy sensor within the cell. The aims of the present work were to analyze a possible effect of MET on healthy rat ovary and on granulosa cells (GCs) in culture. Methods: For in vivo experiments, 21 d old female Sprague Dawley rats received MET (300 mg/kg) dissolved in the drinking water for 15 days (MET group). The control group received drinking water alone. Rats were killed on day 16 and the ovaries removed. Proteins were extracted for western blot analysis. For in vitro experiments, Sprague Dawley rats (21 d) were injected subcutaneously with diethylstilbestrol (1mg/rat) daily for three days. GCs were isolated by percoll gradient. GCs were stimulated with MET (0.01 ng/ml) with or without the organic cation transporter (OCT) inhibitor cimetidine (CIM). Cells were harvested 48 h later and prote ins extracted. One Way ANOVA or t-test were used. p-AMPK was increased in the rat ovaries (p<0.05) and in GCs after stimulation with MET (p<0.05) while VEGF was decreased (p<0.05). Inhibition of OCTs by CIM reversed these effects (p<0.05 compared with MET). No changes in Angiopoietin 1 and 2 were found either in vivo or in vitro. Our results suggest that MET acts directly on ovarian cells regulating cell metabolism and VEGF expression, entering the cells through OCTs. Our findings are relevant to optimize PCOS fertility treatment and to explore direct ovarian MET actions in other female pathologies. These results provide new evidence to explain the effect of MET on infertility treatments.
Fil: Velazquez, Candela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Di Pietro, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Pascuali, Natalia Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Parborell, Maria Fernanda Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Abramovich, Dalhia Nurit. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Materia
METFORMIN
OVARY
PCOS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/243739
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Direct effect of metformin on healthy ovarian cellsVelazquez, CandelaDi Pietro, MarianaPascuali, Natalia MarisaParborell, Maria Fernanda AgustinaAbramovich, Dalhia NuritMETFORMINOVARYPCOShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Metformin (MET) is an oral antihyperglycemic drug introduced in the treatment of polycystic ovary syndrome (PCOS) to manage hyperglycemia. PCOS is a common disorder that affects women in reproductive age. MET improves ovulation, pregnancy and live birth rates in patients with PCOS. The mechanism by which MET of these effects are not fully understood. MET primary mechanism of action is through the activation of the AMP-activated protein kinase (AMPK), which acts as an energy sensor within the cell. The aims of the present work were to analyze a possible effect of MET on healthy rat ovary and on granulosa cells (GCs) in culture. Methods: For in vivo experiments, 21 d old female Sprague Dawley rats received MET (300 mg/kg) dissolved in the drinking water for 15 days (MET group). The control group received drinking water alone. Rats were killed on day 16 and the ovaries removed. Proteins were extracted for western blot analysis. For in vitro experiments, Sprague Dawley rats (21 d) were injected subcutaneously with diethylstilbestrol (1mg/rat) daily for three days. GCs were isolated by percoll gradient. GCs were stimulated with MET (0.01 ng/ml) with or without the organic cation transporter (OCT) inhibitor cimetidine (CIM). Cells were harvested 48 h later and prote ins extracted. One Way ANOVA or t-test were used. p-AMPK was increased in the rat ovaries (p<0.05) and in GCs after stimulation with MET (p<0.05) while VEGF was decreased (p<0.05). Inhibition of OCTs by CIM reversed these effects (p<0.05 compared with MET). No changes in Angiopoietin 1 and 2 were found either in vivo or in vitro. Our results suggest that MET acts directly on ovarian cells regulating cell metabolism and VEGF expression, entering the cells through OCTs. Our findings are relevant to optimize PCOS fertility treatment and to explore direct ovarian MET actions in other female pathologies. These results provide new evidence to explain the effect of MET on infertility treatments.Fil: Velazquez, Candela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Di Pietro, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pascuali, Natalia Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Parborell, Maria Fernanda Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Abramovich, Dalhia Nurit. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaLXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioFundación Revista Medicina2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/243739Direct effect of metformin on healthy ovarian cells; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 261-2610025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol79-19/s4/vol79_s4.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:45Zoai:ri.conicet.gov.ar:11336/243739instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:11:46.376CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Direct effect of metformin on healthy ovarian cells
title Direct effect of metformin on healthy ovarian cells
spellingShingle Direct effect of metformin on healthy ovarian cells
Velazquez, Candela
METFORMIN
OVARY
PCOS
title_short Direct effect of metformin on healthy ovarian cells
title_full Direct effect of metformin on healthy ovarian cells
title_fullStr Direct effect of metformin on healthy ovarian cells
title_full_unstemmed Direct effect of metformin on healthy ovarian cells
title_sort Direct effect of metformin on healthy ovarian cells
dc.creator.none.fl_str_mv Velazquez, Candela
Di Pietro, Mariana
Pascuali, Natalia Marisa
Parborell, Maria Fernanda Agustina
Abramovich, Dalhia Nurit
author Velazquez, Candela
author_facet Velazquez, Candela
Di Pietro, Mariana
Pascuali, Natalia Marisa
Parborell, Maria Fernanda Agustina
Abramovich, Dalhia Nurit
author_role author
author2 Di Pietro, Mariana
Pascuali, Natalia Marisa
Parborell, Maria Fernanda Agustina
Abramovich, Dalhia Nurit
author2_role author
author
author
author
dc.subject.none.fl_str_mv METFORMIN
OVARY
PCOS
topic METFORMIN
OVARY
PCOS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Metformin (MET) is an oral antihyperglycemic drug introduced in the treatment of polycystic ovary syndrome (PCOS) to manage hyperglycemia. PCOS is a common disorder that affects women in reproductive age. MET improves ovulation, pregnancy and live birth rates in patients with PCOS. The mechanism by which MET of these effects are not fully understood. MET primary mechanism of action is through the activation of the AMP-activated protein kinase (AMPK), which acts as an energy sensor within the cell. The aims of the present work were to analyze a possible effect of MET on healthy rat ovary and on granulosa cells (GCs) in culture. Methods: For in vivo experiments, 21 d old female Sprague Dawley rats received MET (300 mg/kg) dissolved in the drinking water for 15 days (MET group). The control group received drinking water alone. Rats were killed on day 16 and the ovaries removed. Proteins were extracted for western blot analysis. For in vitro experiments, Sprague Dawley rats (21 d) were injected subcutaneously with diethylstilbestrol (1mg/rat) daily for three days. GCs were isolated by percoll gradient. GCs were stimulated with MET (0.01 ng/ml) with or without the organic cation transporter (OCT) inhibitor cimetidine (CIM). Cells were harvested 48 h later and prote ins extracted. One Way ANOVA or t-test were used. p-AMPK was increased in the rat ovaries (p<0.05) and in GCs after stimulation with MET (p<0.05) while VEGF was decreased (p<0.05). Inhibition of OCTs by CIM reversed these effects (p<0.05 compared with MET). No changes in Angiopoietin 1 and 2 were found either in vivo or in vitro. Our results suggest that MET acts directly on ovarian cells regulating cell metabolism and VEGF expression, entering the cells through OCTs. Our findings are relevant to optimize PCOS fertility treatment and to explore direct ovarian MET actions in other female pathologies. These results provide new evidence to explain the effect of MET on infertility treatments.
Fil: Velazquez, Candela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Di Pietro, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Pascuali, Natalia Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Parborell, Maria Fernanda Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Abramovich, Dalhia Nurit. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
description Metformin (MET) is an oral antihyperglycemic drug introduced in the treatment of polycystic ovary syndrome (PCOS) to manage hyperglycemia. PCOS is a common disorder that affects women in reproductive age. MET improves ovulation, pregnancy and live birth rates in patients with PCOS. The mechanism by which MET of these effects are not fully understood. MET primary mechanism of action is through the activation of the AMP-activated protein kinase (AMPK), which acts as an energy sensor within the cell. The aims of the present work were to analyze a possible effect of MET on healthy rat ovary and on granulosa cells (GCs) in culture. Methods: For in vivo experiments, 21 d old female Sprague Dawley rats received MET (300 mg/kg) dissolved in the drinking water for 15 days (MET group). The control group received drinking water alone. Rats were killed on day 16 and the ovaries removed. Proteins were extracted for western blot analysis. For in vitro experiments, Sprague Dawley rats (21 d) were injected subcutaneously with diethylstilbestrol (1mg/rat) daily for three days. GCs were isolated by percoll gradient. GCs were stimulated with MET (0.01 ng/ml) with or without the organic cation transporter (OCT) inhibitor cimetidine (CIM). Cells were harvested 48 h later and prote ins extracted. One Way ANOVA or t-test were used. p-AMPK was increased in the rat ovaries (p<0.05) and in GCs after stimulation with MET (p<0.05) while VEGF was decreased (p<0.05). Inhibition of OCTs by CIM reversed these effects (p<0.05 compared with MET). No changes in Angiopoietin 1 and 2 were found either in vivo or in vitro. Our results suggest that MET acts directly on ovarian cells regulating cell metabolism and VEGF expression, entering the cells through OCTs. Our findings are relevant to optimize PCOS fertility treatment and to explore direct ovarian MET actions in other female pathologies. These results provide new evidence to explain the effect of MET on infertility treatments.
publishDate 2019
dc.date.none.fl_str_mv 2019
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status_str publishedVersion
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dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/243739
Direct effect of metformin on healthy ovarian cells; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 261-261
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/243739
identifier_str_mv Direct effect of metformin on healthy ovarian cells; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 261-261
0025-7680
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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publisher.none.fl_str_mv Fundación Revista Medicina
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