Bioinformatic analysis confirms differences in circular RNA expression profiles of cumulus cells between patients with ovarian and peritoneal endometriosis-associated infertility

Xiaodi Huang, Qi Yu
Frontiers in endocrinology · 2023 · vol. 14 , pp. 1137235 · doi:10.3389/fendo.2023.1137235 · PMID:37008951 · W4324373002
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

High-throughput sequencing and bioinformatic analysis of cumulus cells identified distinct circular RNA expression profiles in ovarian versus peritoneal endometriosis-associated infertility, highlighting unique and common circRNAs and enriched signaling pathways.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This study compared circular RNA (circRNA) expression profiles in cumulus cells collected from patients with ovarian endometriosis-associated infertility (OEM, n=3), peritoneal endometriosis-associated infertility (PEM, n=3), and tubal factor infertility controls (TFI, n=3) using high-throughput RNA sequencing, followed by qRT-PCR validation of seven candidates in an expanded set of 30 samples. Across nine samples, 11,833 circRNAs were detected; differentially expressed circRNAs numbered 130 (OEM vs TFI), 71 (PEM vs TFI), and 191 (OEM vs PEM), with 11 circRNAs common to OEM and PEM and additional phenotype-specific unique circRNAs identified. Bioinformatic functional analysis of circRNA-targeted genes showed enrichment of apoptosis, PI3K-AKT, and p53 pathways in PEM–TFI comparisons and JAK–STAT and TGF-β-related pathways in PEM–OEM comparisons, alongside circRNA–miRNA–mRNA network construction, while a major limitation was that miRNA sequencing was not performed because of insufficient RNA to build miRNA libraries. This paper is centrally about endometriosis — it profiles cumulus-cell circRNA differences between ovarian and peritoneal endometriosis-associated infertility and relates those molecular signatures to distinct effects on oocyte-linked pathways.

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Abstract

Endometriosis has a detrimental effect on oocyte quality, and ovarian endometriosis (OEM) and peritoneal endometriosis (PEM) may have different effects on female fertility. Therefore, we conducted a study to explore the circular RNA (circRNA) expression profiles of cumulus cells (CCs) in patients with OEM (n = 3), PEM (n = 3), and tubal factor infertility (TFI, n = 3) using high-throughput sequencing techniques and attempted to identify common and unique circRNAs in the OEM and PEM groups. The CIRCexplorer2 program was used to identify circRNAs. Seven candidate circRNAs were validated in 30 samples using quantitative real-time polymerase chain reaction (qRT-PCR). Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to annotate the function of circRNA-targeted genes, which were verified by sequencing results and constructed circRNA-miRNA-mRNA networks. A total of 11833 circRNAs were identified in nine samples. The numbers of differentially expressed circRNAs between the OEM and TFI groups, PEM and TFI groups, and OEM and PEM groups were 130, 71, and 191, respectively. After taking intersections, 11 circRNAs were considered common circRNAs in the OEM and PEM groups; 39 circRNAs in the OEM group and 17 circRNAs in the PEM group were identified as unique key circRNAs. During qRT-PCR validation, hsa_circ_0003638 was significantly upregulated in the PEM group compared to that in the OEM and TFI groups. Functional analysis of circRNA-targeted genes revealed that apoptosis, PI3K-AKT, and p53 signaling pathways were enriched in the PEM-TFI comparison groups, whereas the functions of target genes involved in the JAK-STAT and TGF-β signaling pathways were enriched in the PEM-OEM comparison groups. Our findings confirmed differences in circRNA expression profiles of CCs between patients with OEM and PEM infertility and provide new insights into the different effects of various endometriosis phenotypes on oocytes.

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Condition tags

mesh:D004715endometriosisinfertility

MeSH descriptors

Computational Biology Computational Biology Computational Biology Computational Biology Computational Biology Computational Biology Computational Biology Computational Biology Computational Biology Computational Biology Computational Biology Computational Biology Computational Biology Computational Biology Computational Biology Computational Biology Computational Biology Endometriosis Endometriosis Endometriosis

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