Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process.
Animals
Anti-Mullerian Hormone
/ pharmacology
Case-Control Studies
DNA Methylation
/ drug effects
Disease Models, Animal
Epigenesis, Genetic
Female
Genetic Predisposition to Disease
Humans
Luteinizing Hormone
/ blood
Male
Mice
Mice, Inbred C57BL
Mixed Function Oxygenases
/ genetics
Ovary
/ metabolism
Polycystic Ovary Syndrome
/ drug therapy
Prenatal Care
Proto-Oncogene Proteins
/ genetics
S-Adenosylmethionine
/ pharmacology
Transcriptome
/ drug effects
AMH
PCOS
developmental programming
epigenetics
fertility
inheritance
metabolic disorder
methylation
neuroendocrine
transgenerational
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
02 03 2021
02 03 2021
Historique:
received:
06
08
2020
revised:
20
11
2020
accepted:
05
01
2021
pubmed:
5
2
2021
medline:
27
1
2022
entrez:
4
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33539777
pii: S1550-4131(21)00004-8
doi: 10.1016/j.cmet.2021.01.004
pmc: PMC7928942
pii:
doi:
Substances chimiques
Proto-Oncogene Proteins
0
S-Adenosylmethionine
7LP2MPO46S
Anti-Mullerian Hormone
80497-65-0
Luteinizing Hormone
9002-67-9
Mixed Function Oxygenases
EC 1.-
TET1 protein, human
EC 1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
513-530.e8Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests P.G., N.E.H.M., I.P., A.-L.B., and V.P. disclose that they are inventors of a submitted patent application by the INSERM (Institut National de la Santé et de la Recherche Médicale) covering methods and kits for diagnostic and treatment of PCOS. All other authors do not have competing interests.
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