Metformin regulates ovarian angiogenesis and follicular development in a female polycystic ovary syndrome rat model

Polycystic ovary syndrome (PCOS) is a frequent pathology that affects more than 5% of women of reproductive age. Among other heterogeneous symptoms, PCOS is characterized by abnormalities in angiogenesis. Metformin has been introduced in the treatment of PCOS to manage insulin resistance and hypergl...

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Autores principales:	Di Pietro, M., Parborell, F., Irusta, G., Pascuali, N., Bas, D., Bianchi, M.S., Tesone, M., Abramovich, D.
Formato:	JOUR
Materias:	angiopoietin 1 angiopoietin 2 insulin metformin platelet derived growth factor B platelet derived growth factor D prasterone vasculotropin vasculotropin receptor 2 angiogenesis modulator platelet derived growth factor vasculotropin A angiogenesis animal experiment animal model Article birth rate cell structure controlled study corpus luteum female glucose metabolism hyperglycemia insulin blood level insulin resistance live birth nonhuman ovary follicle cell ovary polycystic disease ovulation pregnancy priority journal protein expression rat animal blood drug effects metabolism Neovascularization, Pathologic ovary follicle pathophysiology Polycystic Ovary Syndrome Sprague Dawley rat Angiogenesis Modulating Agents Angiopoietin-1 Angiopoietin-2 Animals Dehydroepiandrosterone Female Insulin Insulin Resistance Metformin Ovarian Follicle Platelet-Derived Growth Factor Rats Rats, Sprague-Dawley Vascular Endothelial Growth Factor A
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00137227_v156_n4_p1453_DiPietro
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_00137227_v156_n4_p1453_DiPietro
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spelling	todo:paper_00137227_v156_n4_p1453_DiPietro2023-10-03T14:11:24Z Metformin regulates ovarian angiogenesis and follicular development in a female polycystic ovary syndrome rat model Di Pietro, M. Parborell, F. Irusta, G. Pascuali, N. Bas, D. Bianchi, M.S. Tesone, M. Abramovich, D. angiopoietin 1 angiopoietin 2 insulin metformin platelet derived growth factor B platelet derived growth factor D prasterone vasculotropin vasculotropin receptor 2 angiogenesis modulator angiopoietin 1 angiopoietin 2 metformin platelet derived growth factor prasterone vasculotropin A angiogenesis animal experiment animal model Article birth rate cell structure controlled study corpus luteum female glucose metabolism hyperglycemia insulin blood level insulin resistance live birth nonhuman ovary follicle cell ovary polycystic disease ovulation pregnancy priority journal protein expression rat animal blood drug effects metabolism Neovascularization, Pathologic ovary follicle pathophysiology Polycystic Ovary Syndrome Sprague Dawley rat Angiogenesis Modulating Agents Angiopoietin-1 Angiopoietin-2 Animals Dehydroepiandrosterone Female Insulin Insulin Resistance Metformin Neovascularization, Pathologic Ovarian Follicle Platelet-Derived Growth Factor Polycystic Ovary Syndrome Rats Rats, Sprague-Dawley Vascular Endothelial Growth Factor A Polycystic ovary syndrome (PCOS) is a frequent pathology that affects more than 5% of women of reproductive age. Among other heterogeneous symptoms, PCOS is characterized by abnormalities in angiogenesis. Metformin has been introduced in the treatment of PCOS to manage insulin resistance and hyperglycemia. Besides its metabolic effects, metformin has been shown to improve ovulation, pregnancy and live birth rates in PCOS patients. In the present study, we used a dehydroepiandrosterone-induced PCOS rat model to analyze the effect of metformin administrationon ovarian angiogenesis.Wefound that metformin was able to restore the increased levels of vascular endothelial growth factor, angiopoietin (ANGPT)1, and ANGPT1/ANGPT2 ratio and the decreased levels of platelet-derived growth factor B and platelet-derived growth factor D observed in the dehydroepiandrosterone-treated rats. These effects could take place, at least in part, through a decrease in the levels of serum insulin. We also found an improvement in follicular development, with a lower percentage of small follicles and cysts and a higher percentage of antral follicles and corpora lutea after metformin administration. The improvement in ovarian angiogenesis is likely to restore the accumulation of small follicles observed in PCOS rats and to reduce cyst formation, thus improving follicular development and the percentage of corpora lutea. These results open new insights into the study of metformin action not only in glucose metabolism but also in ovarian dysfunction in PCOS women. Copyright © 2015 by the Endocrine Society. Fil:Di Pietro, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Parborell, F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Irusta, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Bianchi, M.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Tesone, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Abramovich, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00137227_v156_n4_p1453_DiPietro
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	angiopoietin 1 angiopoietin 2 insulin metformin platelet derived growth factor B platelet derived growth factor D prasterone vasculotropin vasculotropin receptor 2 angiogenesis modulator angiopoietin 1 angiopoietin 2 metformin platelet derived growth factor prasterone vasculotropin A angiogenesis animal experiment animal model Article birth rate cell structure controlled study corpus luteum female glucose metabolism hyperglycemia insulin blood level insulin resistance live birth nonhuman ovary follicle cell ovary polycystic disease ovulation pregnancy priority journal protein expression rat animal blood drug effects metabolism Neovascularization, Pathologic ovary follicle pathophysiology Polycystic Ovary Syndrome Sprague Dawley rat Angiogenesis Modulating Agents Angiopoietin-1 Angiopoietin-2 Animals Dehydroepiandrosterone Female Insulin Insulin Resistance Metformin Neovascularization, Pathologic Ovarian Follicle Platelet-Derived Growth Factor Polycystic Ovary Syndrome Rats Rats, Sprague-Dawley Vascular Endothelial Growth Factor A
spellingShingle	angiopoietin 1 angiopoietin 2 insulin metformin platelet derived growth factor B platelet derived growth factor D prasterone vasculotropin vasculotropin receptor 2 angiogenesis modulator angiopoietin 1 angiopoietin 2 metformin platelet derived growth factor prasterone vasculotropin A angiogenesis animal experiment animal model Article birth rate cell structure controlled study corpus luteum female glucose metabolism hyperglycemia insulin blood level insulin resistance live birth nonhuman ovary follicle cell ovary polycystic disease ovulation pregnancy priority journal protein expression rat animal blood drug effects metabolism Neovascularization, Pathologic ovary follicle pathophysiology Polycystic Ovary Syndrome Sprague Dawley rat Angiogenesis Modulating Agents Angiopoietin-1 Angiopoietin-2 Animals Dehydroepiandrosterone Female Insulin Insulin Resistance Metformin Neovascularization, Pathologic Ovarian Follicle Platelet-Derived Growth Factor Polycystic Ovary Syndrome Rats Rats, Sprague-Dawley Vascular Endothelial Growth Factor A Di Pietro, M. Parborell, F. Irusta, G. Pascuali, N. Bas, D. Bianchi, M.S. Tesone, M. Abramovich, D. Metformin regulates ovarian angiogenesis and follicular development in a female polycystic ovary syndrome rat model
topic_facet	angiopoietin 1 angiopoietin 2 insulin metformin platelet derived growth factor B platelet derived growth factor D prasterone vasculotropin vasculotropin receptor 2 angiogenesis modulator angiopoietin 1 angiopoietin 2 metformin platelet derived growth factor prasterone vasculotropin A angiogenesis animal experiment animal model Article birth rate cell structure controlled study corpus luteum female glucose metabolism hyperglycemia insulin blood level insulin resistance live birth nonhuman ovary follicle cell ovary polycystic disease ovulation pregnancy priority journal protein expression rat animal blood drug effects metabolism Neovascularization, Pathologic ovary follicle pathophysiology Polycystic Ovary Syndrome Sprague Dawley rat Angiogenesis Modulating Agents Angiopoietin-1 Angiopoietin-2 Animals Dehydroepiandrosterone Female Insulin Insulin Resistance Metformin Neovascularization, Pathologic Ovarian Follicle Platelet-Derived Growth Factor Polycystic Ovary Syndrome Rats Rats, Sprague-Dawley Vascular Endothelial Growth Factor A
description	Polycystic ovary syndrome (PCOS) is a frequent pathology that affects more than 5% of women of reproductive age. Among other heterogeneous symptoms, PCOS is characterized by abnormalities in angiogenesis. Metformin has been introduced in the treatment of PCOS to manage insulin resistance and hyperglycemia. Besides its metabolic effects, metformin has been shown to improve ovulation, pregnancy and live birth rates in PCOS patients. In the present study, we used a dehydroepiandrosterone-induced PCOS rat model to analyze the effect of metformin administrationon ovarian angiogenesis.Wefound that metformin was able to restore the increased levels of vascular endothelial growth factor, angiopoietin (ANGPT)1, and ANGPT1/ANGPT2 ratio and the decreased levels of platelet-derived growth factor B and platelet-derived growth factor D observed in the dehydroepiandrosterone-treated rats. These effects could take place, at least in part, through a decrease in the levels of serum insulin. We also found an improvement in follicular development, with a lower percentage of small follicles and cysts and a higher percentage of antral follicles and corpora lutea after metformin administration. The improvement in ovarian angiogenesis is likely to restore the accumulation of small follicles observed in PCOS rats and to reduce cyst formation, thus improving follicular development and the percentage of corpora lutea. These results open new insights into the study of metformin action not only in glucose metabolism but also in ovarian dysfunction in PCOS women. Copyright © 2015 by the Endocrine Society.
format	JOUR
author	Di Pietro, M. Parborell, F. Irusta, G. Pascuali, N. Bas, D. Bianchi, M.S. Tesone, M. Abramovich, D.
author_facet	Di Pietro, M. Parborell, F. Irusta, G. Pascuali, N. Bas, D. Bianchi, M.S. Tesone, M. Abramovich, D.
author_sort	Di Pietro, M.
title	Metformin regulates ovarian angiogenesis and follicular development in a female polycystic ovary syndrome rat model
title_short	Metformin regulates ovarian angiogenesis and follicular development in a female polycystic ovary syndrome rat model
title_full	Metformin regulates ovarian angiogenesis and follicular development in a female polycystic ovary syndrome rat model
title_fullStr	Metformin regulates ovarian angiogenesis and follicular development in a female polycystic ovary syndrome rat model
title_full_unstemmed	Metformin regulates ovarian angiogenesis and follicular development in a female polycystic ovary syndrome rat model
title_sort	metformin regulates ovarian angiogenesis and follicular development in a female polycystic ovary syndrome rat model
url	http://hdl.handle.net/20.500.12110/paper_00137227_v156_n4_p1453_DiPietro
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_version_	1807316748731416576

Metformin regulates ovarian angiogenesis and follicular development in a female polycystic ovary syndrome rat model

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