Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process.
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.
Key words
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