Causal inference of inflammatory proteins in infertility: a Mendelian randomization study
BackgroundInfertility affects 8-12% of couples globally, manifesting as a complex reproductive disorder with varied causes, negatively impacting emotional, physical, and social well-being. Inflammation is implicated in many diseases, including male and female infertility.MethodsThis study employed M...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1448530/full |
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| author | Peng Chen Sha Ni Ling Ou-Yang |
| author_facet | Peng Chen Sha Ni Ling Ou-Yang |
| author_sort | Peng Chen |
| collection | DOAJ |
| description | BackgroundInfertility affects 8-12% of couples globally, manifesting as a complex reproductive disorder with varied causes, negatively impacting emotional, physical, and social well-being. Inflammation is implicated in many diseases, including male and female infertility.MethodsThis study employed Mendelian randomization (MR) with two-sample, bidirectional, and mediation approaches to explore the relationship between circulating inflammatory proteins and infertility. Causal analysis was conducted using inverse variance-weighted (IVW) and MR-Egger regression, supplemented by enrichment analysis, protein-protein interaction (PPI) network exploration, and drug signature analysis.ResultsOur findings identified a significant positive correlation between C-X-C motif chemokine 6 (CXCL6) and male infertility, positioning CXCL6 as a potential therapeutic target or biomarker. No causal links were detected between circulating inflammatory proteins and female infertility post-FDR adjustment. Minor mediation effects were observed for metabolites such as androstenediol monosulfate, arachidonoylcholine, and serum phosphate to glycerol ratio. Cytokine-related pathways emerged as significant in both male and female infertility. Gene-drug interaction analysis highlighted the need for further investigation of pioglitazone in treating female infertility.ConclusionThis study establishes a potentially causal relationship between CXCL6 and male infertility, suggesting its potential as a drug target or molecular biomarker. The integrative approach combining causal inference with molecular pathway and drug interaction analysis opens new avenues for understanding and treating infertility. |
| format | Article |
| id | doaj-art-bc85c097563f4b5ba668232b20485e8c |
| institution | OA Journals |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj-art-bc85c097563f4b5ba668232b20485e8c2025-08-20T02:15:40ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-02-011610.3389/fendo.2025.14485301448530Causal inference of inflammatory proteins in infertility: a Mendelian randomization studyPeng ChenSha NiLing Ou-YangBackgroundInfertility affects 8-12% of couples globally, manifesting as a complex reproductive disorder with varied causes, negatively impacting emotional, physical, and social well-being. Inflammation is implicated in many diseases, including male and female infertility.MethodsThis study employed Mendelian randomization (MR) with two-sample, bidirectional, and mediation approaches to explore the relationship between circulating inflammatory proteins and infertility. Causal analysis was conducted using inverse variance-weighted (IVW) and MR-Egger regression, supplemented by enrichment analysis, protein-protein interaction (PPI) network exploration, and drug signature analysis.ResultsOur findings identified a significant positive correlation between C-X-C motif chemokine 6 (CXCL6) and male infertility, positioning CXCL6 as a potential therapeutic target or biomarker. No causal links were detected between circulating inflammatory proteins and female infertility post-FDR adjustment. Minor mediation effects were observed for metabolites such as androstenediol monosulfate, arachidonoylcholine, and serum phosphate to glycerol ratio. Cytokine-related pathways emerged as significant in both male and female infertility. Gene-drug interaction analysis highlighted the need for further investigation of pioglitazone in treating female infertility.ConclusionThis study establishes a potentially causal relationship between CXCL6 and male infertility, suggesting its potential as a drug target or molecular biomarker. The integrative approach combining causal inference with molecular pathway and drug interaction analysis opens new avenues for understanding and treating infertility.https://www.frontiersin.org/articles/10.3389/fendo.2025.1448530/fullinfertilityMendelian randomizationdrug targetmolecular biomarkerCXCL6 |
| spellingShingle | Peng Chen Sha Ni Ling Ou-Yang Causal inference of inflammatory proteins in infertility: a Mendelian randomization study Frontiers in Endocrinology infertility Mendelian randomization drug target molecular biomarker CXCL6 |
| title | Causal inference of inflammatory proteins in infertility: a Mendelian randomization study |
| title_full | Causal inference of inflammatory proteins in infertility: a Mendelian randomization study |
| title_fullStr | Causal inference of inflammatory proteins in infertility: a Mendelian randomization study |
| title_full_unstemmed | Causal inference of inflammatory proteins in infertility: a Mendelian randomization study |
| title_short | Causal inference of inflammatory proteins in infertility: a Mendelian randomization study |
| title_sort | causal inference of inflammatory proteins in infertility a mendelian randomization study |
| topic | infertility Mendelian randomization drug target molecular biomarker CXCL6 |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1448530/full |
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