Differential transcriptional profiles of human cumulus granulosa cells in patients with diminished ovarian reserve.

PURPOSE: This study compared the gene expression profiles of cumulus granulosa cells in patients with diminished ovarian reserve and those with normal ovarian reserves to identify genes that may be involved in the pathogenesis of diminished ovarian reserve.

METHODS

After retrieval of the cumulus-oocyte complex, the cumulus granulosa cells that surrounded the oocytes of 25 patients with diminished ovarian reserve and 25 patients with normal ovarian reserves were removed by mechanical stripping. Extraction of RNA from the cumulus granulosa cells was for RNA sequencing and analysis. RT-PCR was used to confirm the candidate genes. Statistical analysis was performed using student's t test.

RESULTS

A total of 294 upregulated genes and 336 downregulated genes were identified in the POSEIDON patients relative to the normal ovarian reserve group. Bioinformatic analysis showed that the downregulated genes were highly enriched in the Wnt signaling pathway, negative regulation of stress fiber assembly, and cell chemotaxis, while the upregulated genes were highly enriched in functions associated with the regulation of interleukin-5 production and regulation of immune system processes. According to the differential expression levels and their potential functions, IL1RL1, IL33, SFRP4, and S1PR1 were validated by quantitative RT-PCR. The results of RT-PCR were consistent with those of RNA sequencing.

CONCLUSION

Expression of IL1RL1, IL33, SFRP4, and S1PR1 in the cumulus granulosa cells may be involved in the pathogenesis of diminished ovarian reserve.