RGD Reference Report - A molecular mechanism underlying ovarian dysfunction of polycystic ovary syndrome: hyperandrogenism induces epigenetic alterations in the granulosa cells. - Rat Genome Database

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A molecular mechanism underlying ovarian dysfunction of polycystic ovary syndrome: hyperandrogenism induces epigenetic alterations in the granulosa cells.

Authors: Qu, F  Wang, FF  Yin, R  Ding, GL  El-Prince, M  Gao, Q  Shi, BW  Pan, HH  Huang, YT  Jin, M  Leung, PC  Sheng, JZ  Huang, HF 
Citation: Qu F, etal., J Mol Med (Berl). 2012 Feb 21.
RGD ID: 5688285
Pubmed: PMID:22349439   (View Abstract at PubMed)
DOI: DOI:10.1007/s00109-012-0881-4   (Journal Full-text)

The objective of this study was to explore whether hyperandrogenism induces epigenetic alterations of peroxisome proliferator-activated receptor gamma 1 (PPARG1), nuclear corepressor 1 (NCOR1), and histone deacetylase 3 (HDAC3) genes in granulosa cells (GCs) of polycystic ovary syndrome (PCOS) women and whether these alterations are involved in the ovarian dysfunction induced by hyperandrogenism. Thirty-two infertile PCOS women and 147 infertile women with tubal blockage were recruited. PCOS women were divided into the hyperandrogenism (HA) PCOS group (n = 13) and nonhyperandrogenism (N-HA) PCOS group (n = 19). Sixty female Sprague-Dawley rats were used for PCOS model establishment. In GCs of HA PCOS women, PPARG1 mRNA expression was lower, whereas NCOR1 and HDAC3 mRNA expression were higher than N-HA PCOS women and controls (P < 0.05). When all women were divided into successful and failed pregnancy subgroups according to the following clinical pregnancy outcome, we found lower PPARG1 mRNA levels and higher NCOR1 and HDAC3 mRNA levels in the failed subgroup of HA PCOS (P < 0.05). Two hypermethylated CpG sites in the PPARG1 promoter and five hypomethylated CpG sites in the NCOR1 promoter were observed only in HA PCOS women (P < 0.01 to P < 0.0005). The acetylation levels of histone H3 at lysine 9 and p21 mRNA expression were decreased in human GCs treated with dihydrotestosterone in vitro (P < 0.05). PCOS rat models also showed alterations of PPARG1, NCOR1, and HDAC3 mRNA expression and methylation changes of PPARG1 and NCOR1, consistent with the results from humans. Hyperandrogenism induces the epigenetic alterations of PPARG1, NCOR1, and HDAC3 in GCs, which are involved in the ovarian dysfunction of HA PCOS.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NCOR1Humanpolycystic ovary syndrome  ISONcor1 (Rattus norvegicus)mRNA:increased expression:ovary (rat)RGD 
Ncor1Ratpolycystic ovary syndrome  IAGP DNA:hypomethylation:promoter:g.218 and 224 (rat)RGD 
Ncor1Ratpolycystic ovary syndrome  IEP mRNA:increased expression:ovary (rat)RGD 
Ncor1Mousepolycystic ovary syndrome  ISONcor1 (Rattus norvegicus)mRNA:increased expression:ovary (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ncor1  (nuclear receptor co-repressor 1)

Genes (Mus musculus)
Ncor1  (nuclear receptor co-repressor 1)

Genes (Homo sapiens)
NCOR1  (nuclear receptor corepressor 1)


Additional Information