The transcriptome of corona radiata cells from individual MІІ oocytes that after ICSI developed to embryos selected for transfer: PCOS women compared to healthy women

Journal of Ovarian Research

Anne Lis Mikkelsen²  Thomas Høst²  Kirstine Belling³  Kho do Nguyen⁴  David Westergaard³  Si Brask Sonne¹  Marie Louise Wissing² 

[1] Institute of Biology, University of Copenhagen, Copenhagen, 2100, Denmark;Department of Gynecology-Obstetrics, Holbaek Fertility Clinic, Holbaek Hospital, Smedelundsgade 60, Holbaek, 4300, Denmark;Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Kemitorvet building 208, Lyngby, 2800, Denmark;DTU Multi Assay Core, Technical University of Denmark DTU, Lyngby, 2800, Denmark

关键词: Oocyte quality;    PCOS;    Gene expression;    Transcriptome;    Corona radiata cells;   

Others  :  1151648
DOI  :  10.1186/s13048-014-0110-6

 received in 2014-06-08, accepted in 2014-11-11,  发布年份 2014

【 摘 要 】

Background

Corona radiata cells (CRCs) refer to the fraction of cumulus cells just adjacent to the oocyte. The CRCs are closely connected to the oocyte throughout maturation and their gene expression profiles might reflect oocyte quality. Polycystic ovary syndrome (PCOS) is a common cause of infertility. It is controversial whether PCOS associate with diminished oocyte quality. The purpose of this study was to compare individual human CRC samples between PCOS patients and controls.

Methods

All patients were stimulated by the long gonadotropin-releasing hormone (GnRH) agonist protocol. The CRC samples originated from individual oocytes developing into embryos selected for transfer. CRCs were isolated in a two-step denudation procedure, separating outer cumulus cells from the inner CRCs. Extracted RNA was amplified and transcriptome profiling was performed with Human Agilent® arrays.

Results

The transcriptomes of CRCs showed no individual genes with significant differential expression between PCOS and controls, but gene set enrichment analysis identified several cell cycle- and DNA replication pathways overexpressed in PCOS CRCs (FDR < 0.05). Five of the genes contributing to the up-regulated cell cycle pathways in the PCOS CRCs were selected for qRT-PCR validation in ten PCOS and ten control CRC samples. qRT-PCR confirmed significant up-regulation in PCOS CRCs of cell cycle progression genes HIST1H4C (FC = 2.7), UBE2C (FC = 2.6) and cell cycle related transcription factor E2F4 (FC = 2.5).

Conclusion

The overexpression of cell cycle-related genes and cell cycle pathways in PCOS CRCs could indicate a disturbed or delayed final maturation and differentiation of the CRCs in response to the human chorionic gonadotropin (hCG) surge. However, this had no effect on the in vitro development of the corresponding embryos. Future studies are needed to clarify whether the up-regulated cell cycle pathways in PCOS CRCs have any clinical implications.

【 授权许可】

   
2014 Wissing et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

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