Polycystic ovarian syndrome (PCOS) and recurrent spontaneous abortion (RSA) are associated with the PI3K-AKT pathway activation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39253602", "kind": "science-record", "revision": 3, "content_hash": "sha256:2a31bd9aa84dacf6150f6a5b14873eaf317107b0b2841eebd6a95db905a4bd65", "created_at": "2026-11-01T20:29:24Z", "updated_at": "2026-11-01T22:12:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Polycystic ovarian syndrome (PCOS) and recurrent spontaneous abortion (RSA) are associated with the PI3K-AKT pathway activation.", "doi": "10.7717/peerj.17950", "pmid": "39253602", "authors": ["Wenjing Lin", "Yuting Wang", "Lei Zheng"], "journal": "PeerJ", "year": 2024, "abstract": "Aims: We aimed to elucidate the mechanism leading to polycystic ovarian syndrome (PCOS) and recurrent spontaneous abortion (RSA).\nBackground: PCOS is an endocrine disorder. Patients with RSA also have a high incidence rate of PCOS, implying that PCOS and RSA may share the same pathological mechanism.\nObjective: The single-cell RNA-seq datasets of PCOS (GSE168404 and GSE193123) and RSA GSE113790 and GSE178535) were downloaded from the Gene Expression Omnibus (GEO) database.\nMethods: Datasets of PSCO and RSA patients were retrieved from the Gene Expression Omnibus (GEO) database. The \"WGCNA\" package was used to determine the module eigengenes associated with the PCOS and RSA phenotypes and the gene functions were analyzed using the \"DAVID\" database. The GSEA analysis was performed in \"clusterProfiler\" package, and key genes in the activated pathways were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Real-time quantitative PCR (RT-qPCR) was conducted to determine the mRNA level. Cell viability and apoptosis were measured by cell counting kit-8 (CCK-8) and flow cytometry, respectively.\nResults: The modules related to PCOS and RSA were sectioned by weighted gene co-expression network analysis (WGCNA) and positive correlation modules of PCOS and RSA were all enriched in angiogenesis and Wnt pathways. The GSEA further revealed that these biological processes of angiogenesis, Wnt and regulation of cell cycle were significantly positively correlated with the PCOS and RSA phenotypes. The intersection of the positive correlation modules of PCOS and RSA contained 80 key genes, which were mainly enriched in kinase-related signal pathways and were significant high-expressed in the disease samples. Subsequently, visualization of these genes including PDGFC, GHR, PRLR and ITGA3 showed that these genes were associated with the PI3K-AKT signal pathway. Moreover, the experimental results showed that PRLR had a higher expression in KGN cells, and that knocking PRLR down suppressed cell viability and promoted apoptosis of KGN cells.\nConclusion: This study revealed the common pathological mechanisms between PCOS and RSA and explored the role of the PI3K-AKT signaling pathway in the two diseases, providing a new direction for the clinical treatment of PCOS and RSA.", "claims": [{"id": "claim-method", "statement": "The “WGCNA” package was used to determine the module eigengenes associated with the PCOS and RSA phenotypes and the gene functions were analyzed using the “DAVID” database. The GSEA analysis was performed in “clusterProfiler” package, and key genes in the activated pathways were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39253602", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "The “WGCNA” package was used to determine the module eigengenes associated with the PCOS and RSA phenotypes and the gene functions were analyzed using the “DAVID” database. The GSEA analysis was performed in “clusterProfiler” package, and key genes in the activated pathways were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are available at GEO: GSE19123, GSE168404, GSE113790, GSE178535.The raw data is available at GitHub and Zenodo:- https://github.com/6Linwenjing/Updated-new-data.git- 6Linwenjing. (2024). 6Linwenjing/Updated-new-data: My updated data (v.1.1.0). Zenodo. https://doi.org/10.5281/zenodo.12198919", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39253602", "locator": "sections[27] \"Additional Information and Declarations\" paragraph 4", "quote": "The datasets generated and/or analyzed during the current study are available at GEO: GSE19123, GSE168404, GSE113790, GSE178535.The raw data is available at GitHub and Zenodo:- https://github.com/6Linwenjing/Updated-new-data.git- 6Linwenjing. (2024). 6Linwenjing/Updated-new-data: My updated data (v.1.1.0). Zenodo. https://doi.org/10.5281/zenodo.12198919"}], "state": "complete"}, {"id": "claim-target-result", "statement": "Weighted gene co-expression network analysis of publicly downloaded PCOS and RSA transcriptomic datasets identified shared disease-associated modules and 80 shared key genes implicating the PI3K-AKT pathway, with PRLR knockdown subsequently reducing KGN-cell viability and migration while increasing apoptosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39253602", "locator": "sections[0] \"Abstract\" paragraph 5", "quote": "The intersection of the positive correlation modules of PCOS and RSA contained 80 key genes, which were mainly enriched in kinase-related signal pathways and were significant high-expressed in the disease samples."}, {"asset": "source:pmid:39253602", "locator": "sections[0] \"Abstract\" paragraph 5", "quote": "Subsequently, visualization of these genes including PDGFC, GHR, PRLR and ITGA3 showed that these genes were associated with the PI3K-AKT signal pathway."}, {"asset": "source:pmid:39253602", "locator": "sections[0] \"Abstract\" paragraph 5", "quote": "Moreover, the experimental results showed that PRLR had a higher expression in KGN cells, and that knocking PRLR down suppressed cell viability and promoted apoptosis of KGN cells."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Weighted gene co-expression network analysis of publicly downloaded PCOS and RSA transcriptomic datasets identified shared disease-associated modules and 80 shared key genes implicating the PI3K-AKT pathway, with PRLR knockdown subsequently reducing KGN-cell viability and migration while increasing apoptosis.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39253602"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE113790"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE113790"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39253602", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.17950", "sha256": "sha256:32984e0077fb5a44508404569a41f0c94dcdbf61e940307a73e946021bc46bbb", "bytes": 31086, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.17950", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11382649", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE113790", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE113790", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE113790", "version": null, "note": "The datasets generated and/or analyzed during the current study are available at GEO: GSE19123, GSE168404, GSE113790, GSE178535.The raw data is available at GitHub and Zenodo:- https://github.com/6Linwenjing/Updated-new-data.git- 6Linwenjing. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE168404", "GSE193123", "GSE113790", "GSE178535"], "resolved_accessions": ["GSE168404", "GSE193123", "GSE113790", "GSE178535"], "statements": ["The datasets generated and/or analyzed during the current study are available at GEO: GSE19123, GSE168404, GSE113790, GSE178535.The raw data is available at GitHub and Zenodo:- https://github.com/6Linwenjing/Updated-new-data.git- 6Linwenjing. (2024). 6Linwenjing/Updated-new-data: My updated data (v.1.1.0). Zenodo. https://doi.org/10.5281/zenodo.12198919"], "basis": "The paper names GSE168404, GSE193123, GSE113790, GSE178535 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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Objective: The single-cell RNA-seq datasets of PCOS (GSE168404 and GSE193123) a"], "order_basis": "paper_text_order:402", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ogical mechanism. Objective: The single-cell RNA-seq datasets of PCOS (GSE168404 and GSE193123) a"], "order_basis": "paper_text_order:413", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["(KEGG) analysis. Real-time quantitative PCR (RT-qPCR) was conducted to determine the mRNA level.", "GG) analysis. Real-time quantitative PCR (RT-qPCR) was conducted to determine the mRNA level.", "opedia of Genes and Genomes (KEGG) analysis. Real-time quantitative PCR (RT-qPCR) was conducted to determine the mRN", "OSE80 and KGN cell lines were measured using RT-qPCR. The results showed that only the transcript"], "order_basis": "paper_text_order:1027", "id": "assay:3"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["determine the mRNA level. Cell viability and apoptosis were measured by cell counting kit-8 (CCK-8)", "down suppressed cell viability and promoted apoptosis of KGN cells. Conclusion: This study reveale", "ptosis were measured by cell counting kit-8 (CCK-8) and flow cytometry, respectively. Results:", "ckdown PRLR in KGN cells (Figs. 7G, 7H). The apoptosis rate was significantly promoted by loss of P"], "order_basis": "paper_text_order:1126", "id": "assay:4"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["measured by cell counting kit-8 (CCK-8) and flow cytometry, respectively. Results: The modules related"], "order_basis": "paper_text_order:1186", "id": "assay:5"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Materials and Methods Cell culture and transfection Human normal ovarian epithelial cell (IOSE80", "trol (Vector) and si-RNA (Sagon, China) were transfected into cells using Lipofectamine 2000 (Invitro", "periments (p < 0.01, Fig. 7E). Functionally, knockdown of PRLR suppressed cell viability compared t", "p (Fig. 7F). Cell migration was inhibited by knockdown PRLR in KGN cells (Figs. 7G, 7H). The apopto"], "order_basis": "paper_text_order:2444", "id": "assay:6"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["China (Shanghai, China). All the cells were cultured in DMEM (Gibco, Waltham, MA, USA) added with fe"], "order_basis": "paper_text_order:2641", "id": "assay:7"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Wilcoxon"], "order_basis": "consumes_earlier_output", "id": "assay:8"}]}