Mitochondrial DNA oxidation and content in different metabolic phenotypes of women with polycystic ovary syndrome

IntroductionPolycystic Ovary Syndrome (PCOS) affects 5-20% of reproductive-aged women. Insulin resistance (IR) is common in PCOS with consequent elevated risks of metabolic disorders and cardiovascular mortality. PCOS and obesity are complex conditions associated with Metabolic Syndrome (MS), contri...

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Main Authors: Mailén Rojo, Hernán Pérez, Andrea Liliana Millán, María Constanza Pautasso, Alejandra Duarte, Giselle Adriana Abruzzese, Alicia Beatriz Motta, Gustavo Daniel Frechtel, Gloria Edith Cerrone
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2024.1501306/full
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author Mailén Rojo
Mailén Rojo
Hernán Pérez
Hernán Pérez
Andrea Liliana Millán
Andrea Liliana Millán
María Constanza Pautasso
Alejandra Duarte
Alejandra Duarte
Giselle Adriana Abruzzese
Alicia Beatriz Motta
Alicia Beatriz Motta
Gustavo Daniel Frechtel
Gustavo Daniel Frechtel
Gustavo Daniel Frechtel
Gloria Edith Cerrone
Gloria Edith Cerrone
author_facet Mailén Rojo
Mailén Rojo
Hernán Pérez
Hernán Pérez
Andrea Liliana Millán
Andrea Liliana Millán
María Constanza Pautasso
Alejandra Duarte
Alejandra Duarte
Giselle Adriana Abruzzese
Alicia Beatriz Motta
Alicia Beatriz Motta
Gustavo Daniel Frechtel
Gustavo Daniel Frechtel
Gustavo Daniel Frechtel
Gloria Edith Cerrone
Gloria Edith Cerrone
author_sort Mailén Rojo
collection DOAJ
description IntroductionPolycystic Ovary Syndrome (PCOS) affects 5-20% of reproductive-aged women. Insulin resistance (IR) is common in PCOS with consequent elevated risks of metabolic disorders and cardiovascular mortality. PCOS and obesity are complex conditions associated with Metabolic Syndrome (MS), contributing to cardiovascular disease and type 2 diabetes mellitus (T2D). Obesity and PCOS exacerbate each other, with central obesity driving metabolic changes. Mitochondrial dysfunction, characterized by oxidative stress and reduced antioxidant capacity, plays a key role in PCOS pathology.MethodsIn our study, we investigated 81 women with PCOS, and 57 control women aged 16 to 46 years old. Relative mitochondrial DNA (mtDNA) content and its oxidation level (8-oxoguanine, 8-OxoG) were determined in peripheral blood leukocytes by the SYBR Green method real-time PCR.ResultsOur findings showed that patients with PCOS had decreased mtDNA content and increased oxidation damage. Stratifying these patients by metabolic profile, revealed a progressive decline in mtDNA content from the normal-weight control group to the MHO-PCOS and MUO-PCOS groups, suggesting that lower mtDNA content is linked to obesity and worse metabolic profile. However, mtDNA oxidation levels did not differ significantly among these groups. Additionally, the decline in mtDNA content and the increase in oxidation levels between controls and patients with PCOS lost significance when these relationships were adjusted for the HOMA index.DiscussionThis finding suggests that IR could be the main factor contributing to mitochondrial dysfunction in PCOS. Maintaining optimal mtDNA copies are crucial for mitochondrial and cell function, suggesting potential therapeutic targets for PCOS-associated metabolic disturbances.
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spelling doaj-art-c20f2a567a6143dcab5ddb475f68b9292025-01-09T05:10:13ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-01-011510.3389/fendo.2024.15013061501306Mitochondrial DNA oxidation and content in different metabolic phenotypes of women with polycystic ovary syndromeMailén Rojo0Mailén Rojo1Hernán Pérez2Hernán Pérez3Andrea Liliana Millán4Andrea Liliana Millán5María Constanza Pautasso6Alejandra Duarte7Alejandra Duarte8Giselle Adriana Abruzzese9Alicia Beatriz Motta10Alicia Beatriz Motta11Gustavo Daniel Frechtel12Gustavo Daniel Frechtel13Gustavo Daniel Frechtel14Gloria Edith Cerrone15Gloria Edith Cerrone16Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Universidad de Buenos Aires, Buenos Aires, ArgentinaInstituto de Inmunología, Genética y Metabolismo (INIGEM), Universidad de Buenos Aires – National Scientific and Technical Research Council (CONICET), Buenos Aires, ArgentinaInstituto de Inmunología, Genética y Metabolismo (INIGEM), Universidad de Buenos Aires – National Scientific and Technical Research Council (CONICET), Buenos Aires, ArgentinaHospital de Clínicas José de San Martin, Servicio de Nutrición, Buenos Aires, ArgentinaFacultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Universidad de Buenos Aires, Buenos Aires, ArgentinaInstituto de Inmunología, Genética y Metabolismo (INIGEM), Universidad de Buenos Aires – National Scientific and Technical Research Council (CONICET), Buenos Aires, ArgentinaInstituto de Inmunología, Genética y Metabolismo (INIGEM), Universidad de Buenos Aires – National Scientific and Technical Research Council (CONICET), Buenos Aires, ArgentinaInstituto de Inmunología, Genética y Metabolismo (INIGEM), Universidad de Buenos Aires – National Scientific and Technical Research Council (CONICET), Buenos Aires, ArgentinaFundación Héctor Alejandro (H.A.) Barceló, Instituto Universitario de Ciencias de la Salud, Buenos Aires, ArgentinaCentro de Estudios Farmacológicos y Botánicos (CEFYBO), Laboratorio de Fisiopatología ovárica, Universidad de Buenos Aires – National Scientific and Technical Research Council (CONICET), Buenos Aires, ArgentinaFundación Héctor Alejandro (H.A.) Barceló, Instituto Universitario de Ciencias de la Salud, Buenos Aires, ArgentinaCentro de Estudios Farmacológicos y Botánicos (CEFYBO), Laboratorio de Fisiopatología ovárica, Universidad de Buenos Aires – National Scientific and Technical Research Council (CONICET), Buenos Aires, ArgentinaInstituto de Inmunología, Genética y Metabolismo (INIGEM), Universidad de Buenos Aires – National Scientific and Technical Research Council (CONICET), Buenos Aires, ArgentinaHospital de Clínicas José de San Martin, Servicio de Nutrición, Buenos Aires, ArgentinaFundación Héctor Alejandro (H.A.) Barceló, Instituto Universitario de Ciencias de la Salud, Buenos Aires, ArgentinaFacultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Universidad de Buenos Aires, Buenos Aires, ArgentinaInstituto de Inmunología, Genética y Metabolismo (INIGEM), Universidad de Buenos Aires – National Scientific and Technical Research Council (CONICET), Buenos Aires, ArgentinaIntroductionPolycystic Ovary Syndrome (PCOS) affects 5-20% of reproductive-aged women. Insulin resistance (IR) is common in PCOS with consequent elevated risks of metabolic disorders and cardiovascular mortality. PCOS and obesity are complex conditions associated with Metabolic Syndrome (MS), contributing to cardiovascular disease and type 2 diabetes mellitus (T2D). Obesity and PCOS exacerbate each other, with central obesity driving metabolic changes. Mitochondrial dysfunction, characterized by oxidative stress and reduced antioxidant capacity, plays a key role in PCOS pathology.MethodsIn our study, we investigated 81 women with PCOS, and 57 control women aged 16 to 46 years old. Relative mitochondrial DNA (mtDNA) content and its oxidation level (8-oxoguanine, 8-OxoG) were determined in peripheral blood leukocytes by the SYBR Green method real-time PCR.ResultsOur findings showed that patients with PCOS had decreased mtDNA content and increased oxidation damage. Stratifying these patients by metabolic profile, revealed a progressive decline in mtDNA content from the normal-weight control group to the MHO-PCOS and MUO-PCOS groups, suggesting that lower mtDNA content is linked to obesity and worse metabolic profile. However, mtDNA oxidation levels did not differ significantly among these groups. Additionally, the decline in mtDNA content and the increase in oxidation levels between controls and patients with PCOS lost significance when these relationships were adjusted for the HOMA index.DiscussionThis finding suggests that IR could be the main factor contributing to mitochondrial dysfunction in PCOS. Maintaining optimal mtDNA copies are crucial for mitochondrial and cell function, suggesting potential therapeutic targets for PCOS-associated metabolic disturbances.https://www.frontiersin.org/articles/10.3389/fendo.2024.1501306/fullobesityoxidative damagemetabolic syndromepolycystic ovary syndromemitochondrial DNA
spellingShingle Mailén Rojo
Mailén Rojo
Hernán Pérez
Hernán Pérez
Andrea Liliana Millán
Andrea Liliana Millán
María Constanza Pautasso
Alejandra Duarte
Alejandra Duarte
Giselle Adriana Abruzzese
Alicia Beatriz Motta
Alicia Beatriz Motta
Gustavo Daniel Frechtel
Gustavo Daniel Frechtel
Gustavo Daniel Frechtel
Gloria Edith Cerrone
Gloria Edith Cerrone
Mitochondrial DNA oxidation and content in different metabolic phenotypes of women with polycystic ovary syndrome
Frontiers in Endocrinology
obesity
oxidative damage
metabolic syndrome
polycystic ovary syndrome
mitochondrial DNA
title Mitochondrial DNA oxidation and content in different metabolic phenotypes of women with polycystic ovary syndrome
title_full Mitochondrial DNA oxidation and content in different metabolic phenotypes of women with polycystic ovary syndrome
title_fullStr Mitochondrial DNA oxidation and content in different metabolic phenotypes of women with polycystic ovary syndrome
title_full_unstemmed Mitochondrial DNA oxidation and content in different metabolic phenotypes of women with polycystic ovary syndrome
title_short Mitochondrial DNA oxidation and content in different metabolic phenotypes of women with polycystic ovary syndrome
title_sort mitochondrial dna oxidation and content in different metabolic phenotypes of women with polycystic ovary syndrome
topic obesity
oxidative damage
metabolic syndrome
polycystic ovary syndrome
mitochondrial DNA
url https://www.frontiersin.org/articles/10.3389/fendo.2024.1501306/full
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