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Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process.
Mimouni, Nour El Houda; Paiva, Isabel; Barbotin, Anne-Laure; Timzoura, Fatima Ezzahra; Plassard, Damien; Le Gras, Stephanie; Ternier, Gaetan; Pigny, Pascal; Catteau-Jonard, Sophie; Simon, Virginie; Prevot, Vincent; Boutillier, Anne-Laurence; Giacobini, Paolo.
Affiliation
  • Mimouni NEH; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172, FHU 1000 days for health, 59000 Lille, France.
  • Paiva I; Université de Strasbourg, UMR 7364 CNRS, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), 12 Rue Goethe, Strasbourg 67000, France.
  • Barbotin AL; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172, FHU 1000 days for health, 59000 Lille, France.
  • Timzoura FE; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172, FHU 1000 days for health, 59000 Lille, France.
  • Plassard D; CNRS UMR 7104, INSERM U1258, GenomEast Platform, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, Illkirch, France.
  • Le Gras S; CNRS UMR 7104, INSERM U1258, GenomEast Platform, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, Illkirch, France.
  • Ternier G; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172, FHU 1000 days for health, 59000 Lille, France.
  • Pigny P; CHU Lille, Service de Biochimie et Hormonologie, Centre de Biologie Pathologie, Lille, France.
  • Catteau-Jonard S; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172, FHU 1000 days for health, 59000 Lille, France; CHU Lille, Service de Gynécologie Médicale, Hôpital Jeanne de Flandre, Lille, France.
  • Simon V; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172, FHU 1000 days for health, 59000 Lille, France; CHU Lille, Service de Gynécologie Médicale, Hôpital Jeanne de Flandre, Lille, France.
  • Prevot V; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172, FHU 1000 days for health, 59000 Lille, France.
  • Boutillier AL; Université de Strasbourg, UMR 7364 CNRS, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), 12 Rue Goethe, Strasbourg 67000, France. Electronic address: laurette@unistra.fr.
  • Giacobini P; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172, FHU 1000 days for health, 59000 Lille, France. Electronic address: paolo.giacobini@inserm.fr.
Cell Metab ; 33(3): 513-530.e8, 2021 03 02.
Article in En | MEDLINE | ID: mdl-33539777
ABSTRACT
Polycystic ovary syndrome (PCOS) is the most common reproductive and metabolic disorder affecting women of reproductive age. PCOS has a strong heritable component, but its pathogenesis has been unclear. Here, we performed RNA sequencing and genome-wide DNA methylation profiling of ovarian tissue from control and third-generation PCOS-like mice. We found that DNA hypomethylation regulates key genes associated with PCOS and that several of the differentially methylated genes are also altered in blood samples from women with PCOS compared with healthy controls. Based on this insight, we treated the PCOS mouse model with the methyl group donor S-adenosylmethionine and found that it corrected their transcriptomic, neuroendocrine, and metabolic defects. These findings show that the transmission of PCOS traits to future generations occurs via an altered landscape of DNA methylation and propose methylome markers as a possible diagnostic landmark for the condition, while also identifying potential candidates for epigenetic-based therapy.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Polycystic Ovary Syndrome / Epigenesis, Genetic Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Animals / Female / Humans / Male Language: En Journal: Cell Metab Journal subject: METABOLISMO Year: 2021 Document type: Article Affiliation country: France

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Polycystic Ovary Syndrome / Epigenesis, Genetic Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Animals / Female / Humans / Male Language: En Journal: Cell Metab Journal subject: METABOLISMO Year: 2021 Document type: Article Affiliation country: France