Pericuesta, EvaLaguna-Barraza, RicardoRamos-Ibeas, PriscilaGutierrez-Arroyo, Julia L.Navarro, Juan A.Vera, KatiaSanjuan, CarlosBaixeras, ElenaRodríguez de Fonseca, FernandoGutierrez-Adan, Alfonso2022-08-022022-08-022020-08-22Pericuesta E, Laguna-Barraza R, Ramos-Ibeas P, Gutierrez-Arroyo JL, Navarro JA, Vera K, et al. D-Chiro-Inositol Treatment Affects Oocyte and Embryo Quality and Improves Glucose Intolerance in Both Aged Mice and Mouse Models of Polycystic Ovarian Syndrome. Int J Mol Sci. 2020 Aug 22;21(17):6049http://hdl.handle.net/10668/3863Polycystic ovarian syndrome (PCOS) is the main cause of female infertility. It is a multifactorial disorder with varying clinical manifestations including metabolic/endocrine abnormalities, hyperandrogenism, and ovarian cysts, among other conditions. D-Chiro-inositol (DCI) is the main treatment available for PCOS in humans. To address some of the mechanisms of this complex disorder and its treatment, this study examines the effect of DCI on reproduction during the development of different PCOS-associated phenotypes in aged females and two mouse models of PCOS. Aged females (8 months old) were treated or not (control) with DCI for 2 months. PCOS models were generated by treatment with dihydrotestosterone (DHT) on Days 16, 17, and 18 of gestation, or by testosterone propionate (TP) treatment on the first day of life. At two months of age, PCOS mice were treated with DCI for 2 months and their reproductive parameters analyzed. No effects of DCI treatment were produced on body weight or ovary/body weight ratio. However, treatment reduced the number of follicles with an atretic cyst-like appearance and improved embryo development in the PCOS models, and also increased implantation rates in both aged and PCOS mice. DCI modified the expression of genes related to oocyte quality, oxidative stress, and luteal sufficiency in cumulus-oocyte complexes (COCs) obtained from the aged and PCOS models. Further, the phosphorylation of AKT, a main metabolic sensor activated by insulin in the liver, was enhanced only in the DHT group, which was the only PCOS model showing glucose intolerance and AKT dephosphorylation. The effect of DCI in the TP model seemed mediated by its influence on oxidative stress and follicle insufficiency. Our results indicate that DCI works in preclinical models of PCOS and offer insight into its mechanism of action when used to treat this infertility-associated syndrome.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Polycystic ovary syndromeD-chiro-inositolOocyteEmbryoFertilityOxidative stressGlucose intoleranceSíndrome del ovario poliquísticoOocitosEstructuras embrionariasFertilidadEstrés oxidativoIntolerancia a la glucosaMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::AgingMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Anatomy::Embryonic Structures::Embryo, Mammalian::BlastocystMedical Subject Headings::Anatomy::Cells::Endocrine Cells::Granulosa Cells::Cumulus CellsMedical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Steroids::Androstanes::Androstanols::DihydrotestosteroneMedical Subject Headings::Diseases::Animal Diseases::Disease Models, AnimalMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression RegulationMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperglycemia::Glucose IntoleranceMedical Subject Headings::Diseases::Female Urogenital Diseases and Pregnancy Complications::Female Urogenital Diseases::Genital Diseases, Female::Infertility::Infertility, FemaleMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Alcohols::Sugar Alcohols::InositolMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Inbred StrainsMedical Subject Headings::Anatomy::Cells::Germ Cells::Ovum::OocytesMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::PhosphorylationMedical Subject Headings::Diseases::Female Urogenital Diseases and Pregnancy Complications::Female Urogenital Diseases::Genital Diseases, Female::Adnexal Diseases::Ovarian Diseases::Ovarian Cysts::Polycystic Ovary SyndromeMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Oncogene Proteins::Proto-Oncogene Proteins::Proto-Oncogene Proteins c-aktMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Gonadal Hormones::Gonadal Steroid Hormones::Testosterone Congeners::Testosterone::Testosterone Propionateresearch article32842637open access10.3390/ijms211760491422-0067PMC7504697