mRNA, lncRNA and Circular RNA Expression Profiles in Granulosa Cells of Infertile Women with Ovarian Endometriosis

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This study profiled mRNA, lncRNA, and circRNA expression in granulosa cells from infertile women with ovarian endometriosis, identifying differentially expressed RNAs and constructing regulatory networks.

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This study examined mRNA, lncRNA, and circular RNA expression profiles in granulosa cells from infertile women with ovarian endometriosis versus tubal factor infertility controls, using RNA sequencing on five endometriosis and five control samples and comparative differential-expression analyses. The authors identified thousands of transcripts overall and found 37 mRNAs, 51 lncRNAs, and 101 circRNAs to be differentially expressed, then constructed lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA competitive endogenous RNA networks from selected differentially expressed RNAs. Gene Ontology and KEGG pathway enrichment indicated differential mRNAs involved in regulation of cell differentiation and cell cycle, with enriched MAPK and FoxO signaling among upregulated mRNAs. A key limitation is the very small sample size (n=5 per group). This paper is centrally about endometriosis-related infertility — it profiles granulosa-cell mRNA, lncRNA, and circRNA expression in ovarian endometriosis.

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Abstract

To explore the expression profiles of mRNAs, long-noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and construct the competitive endogenous RNA networks in granulosa cells (GCs) of infertile women with ovarian endometriosis. RNA sequencing was conducted for RNA expression profiling from GCs of five women with ovarian endometriosis and five with tubal factor infertility. The differential expression of mRNAs, lncRNAs and circRNAs was compared. Then, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed. Finally, the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to determine the role of the differential expression of mRNA. A total of 12,498 mRNAs, 724 lncRNAs and 2269 circRNAs were identified in ovarian endometriosis and controls. 37 mRNAs, 51 lncRNAs and 101 circRNAs were detected to be differentially expressed in women with ovarian endometriosis. Ten lncRNAs and 22 differentially expressed mRNAs were selected to build the lncRNA-miRNA-mRNA network, while 12 circRNAs and four differentially expressed mRNAs were selected to build the circRNA-miRNA-mRNA network. GO analysis suggested that the differentially expressed mRNAs were mainly involved in regulation of cell differentiation, cell cycle while KEGG pathway analysis showed that pathways involved in the MAPK signaling pathway and FoxO signaling pathway were enriched with differentially upregulated mRNAs. We generated mRNAs, lncRNAs and circRNAs expression profiles and identified differentially expressed RNAs of GCs in infertile women with ovarian endometriosis. These findings provide a basis for further understanding of the underlying etiology of endometriosis-related infertility.
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Abstract

To explore the expression profiles of mRNAs, long-noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and construct the competitive endogenous RNA networks in granulosa cells (GCs) of infertile women with ovarian endometriosis. RNA sequencing was conducted for RNA expression profiling from GCs of five women with ovarian endometriosis and five with tubal factor infertility. The differential expression of mRNAs, lncRNAs and circRNAs was compared. Then, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed. Finally, the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to determine the role of the differential expression of mRNA. A total of 12,498 mRNAs, 724 lncRNAs and 2269 circRNAs were identified in ovarian endometriosis and controls. 37 mRNAs, 51 lncRNAs and 101 circRNAs were detected to be differentially expressed in women with ovarian endometriosis. Ten lncRNAs and 22 differentially expressed mRNAs were selected to build the lncRNA–miRNA–mRNA network, while 12 circRNAs and four differentially expressed mRNAs were selected to build the circRNA–miRNA–mRNA network. GO analysis suggested that the differentially expressed mRNAs were mainly involved in regulation of cell differentiation, cell cycle while KEGG pathway analysis showed that pathways involved in the MAPK signaling pathway and FoxO signaling pathway were enriched with differentially upregulated mRNAs. We generated mRNAs, lncRNAs and circRNAs expression profiles and identified differentially expressed RNAs of GCs in infertile women with ovarian endometriosis. These findings provide a basis for further understanding of the underlying etiology of endometriosis-related infertility. Similar content being viewed by others Data Availability The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Code Availability Not applicable. Change history 18 July 2022 This article was updated to fix the tagging of the equal contribution note.

References

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Acknowledgements

We thank Dr. Hongmin Chen for the help in data analysis. We also thank the patients who participated in this study. Funding This research was supported by the Basic and Applied Basic Research Foundation of Guangdong Province of China (No. 2020A1515110791). Author information Authors and Affiliations Contributions Jintao Peng and Xiaoyan Liang designed the experiments. Jiayi Guo performed the experiments and wrote the manuscript. Both Jiayi Guo and Haitao Zeng contributed equally to this study. Jintao Peng and Haitao Zeng performed data analysis and constructed the figures. Tingting Li assisted in the design of the experiments. Jintao Peng and Xiaoyan Liang revised the manuscript. All authors approved the final version of the manuscript for publication. Corresponding authors Ethics declarations Conflict of Interest The authors have no conflicts of interest. Ethics Approval This study was approved by the Ethics Committee of the Six Affiliated Hospital of Sun Yat-sen University(2021ZSLYEC-299). Consent for Publication All patients obtained written informed consent. Consent for Publication Not applicable. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions About this article Cite this article Guo, J., Zeng, H., Li, T. et al. mRNA, lncRNA and Circular RNA Expression Profiles in Granulosa Cells of Infertile Women with Ovarian Endometriosis. Reprod. Sci. 29, 2937–2946 (2022). https://doi.org/10.1007/s43032-022-00966-3 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-022-00966-3

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Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

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