[Molecular characterization of corona radiata cells from patients with diminished ovarian reserve].
OBJECTIVE
Diminished ovarian reserve (DOR) is one of the causes of infertility. In this prospective study, gene expression profiling (GEP) of corona radiata cells (CRC) was performed to identify genes deregulated in DOR patients.


METHODS
Microarray-based GEP of CRC isolated from eight women undergoing IVF was performed to identify genes differentially expressed between patients with normal ovarian reserve and DOR patients. Microfluidic-based quantitative RT-PCR assay were used to validate selected transcripts on 40 independent patients.


RESULTS
Forty-eight transcripts were differentially expressed, including CXXC5 and FOXC1 down regulated in DOR, as well as CTGF, FSTL3, PTGS2 and SOCS2 up regulated in DOR. According to these transcripts, two DOR patients'subgroups (DOR Gr1 and Gr2) were identified. In DOR Gr2 patients, CITED2, CTGF, GAS-1, IRS2, PTGS2, SOCS2, VCAN were expressed at significantly higher levels, and CXXC5, FOXC1, GBP2 and ZMIZ1 at significantly lower level. Eleven of those genes are transcriptional targets of Estrogens and higher baseline oestradiol levels were observed in DOR Gr2 patients (P<0.006).


CONCLUSIONS
Twelve genes deregulated in CRC of DOR patients were identified, which could be involved in DOR pathogenesis. The distinction of a particular subgroup of DOR patients suggests the possibility of deregulation of estrogen response genes.
Laboratoire de biologie de la reproduction, centre hospitalier universitaire, 49933 Angers, France. PaMayPanloup@chu-angers.fr
P
P
May-Panloup
V
V
Ferré-L'Hôtellier
C
C
Morinière
C
C
Marcaillou
S
S
Lemerle
A
A
Coutolleau
P
P
Reynier
P
P
Descamps
P
P
Guardiola
D002352:Carrier Proteins / Q000235:genetics; D055513:Connective Tissue Growth Factor / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D038702:Follistatin-Related Proteins / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007247:Infertility, Female / Q000235:genetics* / Q000378:metabolism; D010049:Ovarian Diseases / Q000235:genetics* / Q000378:metabolism; D006080:Ovarian Follicle / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D014157:Transcription Factors
C526317:CCN2 protein, human; C540448:CXXC5 protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C112743:FOXC1 protein, human; D038702:Follistatin-Related Proteins; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; C106643:SOCS2 protein, human; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D055513:Connective Tissue Growth Factor; D051546:Cyclooxygenase 2