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Updated: May 25, 2026
Collection of Human Follicular Fluid, Follicle Somatic Cells, and Immature Oocytes from Individuals Undergoing In Vitro Fertilization
Published on: October 24, 2025
Molecular characterization of corona radiata cells from patients with diminished ovarian reserve using microarray and
Pascale May-Panloup1, Véronique Ferré-L'Hôtellier, Catherine Morinière
1Laboratoire de Biologie de Reproduction, Centre Hospitalier Universitaire, Angers cedex 9 49933, France. pamaypanloup@chu-angers.fr
Background:
Diminished ovarian reserve (DOR) is one of the causes of infertility in young women. 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 assays were used to validate selected transcripts on 40 independent patients. A principal component analysis was used to identify more homogeneous subgroups of DOR patients. In silico analyses focusing on cis-regulation were performed to refine the interactions between patient's biological characteristics and their GEP.
Results:
Forty-eight transcripts were differentially expressed, including CXXC finger protein 5 (CXXC5), forkhead box C1 (FOXC1) (down-regulated in DOR) as well as connective tissue growth factor (CTGF), follistatin-like 3 (FSTL3), prostaglandin-endoperoxide synthase 2 (PTGS2) and suppressor of cytokine signaling 2 (SOCS2) (up-regulated in DOR). According to these transcripts, two DOR patients' subgroups (DOR Gr1 and Gr2) were identified. In DOR Gr2 patients, C-terminal domain 2 (CITED2), CTGF, growth arrest-specific 1 (GAS1), insulin receptor substrate 2 (IRS2), PTGS2, SOCS2 and Versican (VCAN) were expressed at significantly higher levels and CXXC5, FOXC1, guanylate-binding protein 2 (GBP2) and zinc finger MIZ-domain containing 1 (ZMIZ1) at significantly lower levels. Higher baseline estradiol (E(2)) levels were observed in DOR Gr2 patients (P < 0.006). The in silico analyses suggested that all 11 genes differentially expressed between DOR Gr1 and DOR Gr2 subgroups could be transcriptional targets of estrogen.
Conclusions:
Despite small sample size limitations, 12 genes deregulated in the CRC of DOR patients were identified, which could be involved in DOR pathogenesis. A DOR patient's subgroup with high baseline E(2) levels and deregulated estrogen-responsive genes was also identified.
Insights
Gene expression profiling of corona radiata cells identified 12 deregulated genes in diminished ovarian reserve (DOR) patients, potentially impacting infertility. A subgroup of DOR patients with high estradiol levels and estrogen-responsive genes was also identified.
Area of Science:
- Reproductive biology
- Genomics
- Infertility research
Background:
- Diminished ovarian reserve (DOR) is a significant cause of infertility in young women.
- Understanding the molecular mechanisms underlying DOR is crucial for developing effective treatments.
Purpose of the Study:
- To identify genes deregulated in the corona radiata cells (CRC) of women with DOR using gene expression profiling (GEP).
- To investigate potential subgroups within DOR patients based on gene expression patterns and clinical characteristics.
Main Methods:
- Prospective study involving microarray-based GEP of CRC from women undergoing IVF.
- Validation of selected transcripts using microfluidic-based quantitative RT-PCR assays.
- Principal component analysis and in silico analyses to identify patient subgroups and gene regulatory interactions.
Main Results:
- Forty-eight transcripts were differentially expressed in DOR patients compared to controls.
- Key genes such as CXXC5 and FOXC1 were down-regulated, while CTGF, FSTL3, PTGS2, and SOCS2 were up-regulated in DOR.
- Two DOR subgroups were identified; DOR Gr2 exhibited higher levels of certain genes and lower levels of others, associated with higher baseline estradiol (E2) levels and potentially estrogen-responsive genes.
Conclusions:
- Twelve genes were identified as deregulated in CRC of DOR patients, suggesting their involvement in DOR pathogenesis.
- A distinct DOR subgroup characterized by elevated E2 levels and altered estrogen-responsive gene expression was identified.
- These findings provide novel insights into the molecular heterogeneity of DOR and potential therapeutic targets.
