{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:02:19Z","timestamp":1787580139239,"version":"build-2736575974"},"reference-count":76,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Preventive Medicine Research Foundation of Jiangsu Province","award":["Ym2023003"],"award-info":[{"award-number":["Ym2023003"]}]},{"name":"Preventive Medicine Research Foundation of Jiangsu Province","award":["ZKX24033"],"award-info":[{"award-number":["ZKX24033"]}]},{"DOI":"10.13039\/501100019349","name":"Nanjing Medical Science and Technique Development Foundation","doi-asserted-by":"publisher","award":["Ym2023003"],"award-info":[{"award-number":["Ym2023003"]}],"id":[{"id":"10.13039\/501100019349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019349","name":"Nanjing Medical Science and Technique Development Foundation","doi-asserted-by":"publisher","award":["ZKX24033"],"award-info":[{"award-number":["ZKX24033"]}],"id":[{"id":"10.13039\/501100019349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Bifenthrin (BF) is a widely used pyrethroid pesticide recognized as an endocrine-disrupting chemical (EDC). Previous studies have confirmed that chronic exposure to BF is associated with various health risks. However, its potential association with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) remains unclear. In this study, the potential targets of BF were identified using several databases, including the Comparative Toxicogenomics Database (CTD), TargetNet, GeneCards, SwissTargetPrediction, and STITCH. Differentially expressed genes (DEGs) associated with RIF were obtained from bulk RNA-seq datasets in the GEO database. Candidate targets were identified by intersecting the predicted BF-related targets with the RIF-associated DEGs, followed by functional enrichment analysis using the DAVID and g:Profiler platforms. Subsequently, hub genes were identified based on the STRING database and Cytoscape. A diagnostic model was then constructed based on these hub genes in the RIF cohort and validated in an independent recurrent pregnancy loss (RPL) cohort. Additionally, we performed single-cell type distribution analysis and immune infiltration profiling based on single-cell RNA-seq and bulk RNA-seq data, respectively. Molecular docking analysis using AutoDock Vina was conducted to evaluate the binding affinity between BF and the four hub proteins, as well as several hormone-related receptors. Functional enrichment results indicated that the candidate genes were mainly involved in apoptotic and oxidative stress-related pathways. Ultimately, four hub genes\u2014BCL2, HMOX1, CYCS, and PTGS2\u2014were identified. The diagnostic model based on these genes exhibited good predictive performance in the RIF cohort and was successfully validated in the RPL cohort. Single-cell transcriptomic analysis revealed a significant increase in the proportion of myeloid cells in RPL patients, while immune infiltration analysis showed a consistent downregulation of M2 macrophages in both RIF and RPL. Moreover, molecular docking analysis revealed that BF exhibited high binding affinity to all four hub proteins and demonstrated strong binding potential with multiple hormone receptors, particularly pregnane X receptor (PXR), estrogen receptor \u03b1 (ESR\u03b1), and thyroid hormone receptors (TR). In conclusion, the association of BF with four hub genes and multiple hormone receptors suggests a potential link to immune and endocrine dysregulation observed in RIF and RPL. However, in vivo and in vitro experimental evidence is currently lacking, and further studies are needed to elucidate the mechanisms by which BF may contribute to RIF and RPL.<\/jats:p>","DOI":"10.3390\/toxics13060454","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T06:14:27Z","timestamp":1748585667000},"page":"454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring the Role of Bifenthrin in Recurrent Implantation Failure and Pregnancy Loss Through Network Toxicology and Molecular Docking"],"prefix":"10.3390","volume":"13","author":[{"given":"Shengyuan","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Children\u2019s Healthcare Hospital, Nanjing 210004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Children\u2019s Healthcare Hospital, Nanjing 210004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Children\u2019s Healthcare Hospital, Nanjing 210004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Public Health, Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Chidren\u2019s Healthcare Hospital, Nanjing 210004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Children\u2019s Healthcare Hospital, Nanjing 210004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaipeng","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Public Health, Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Chidren\u2019s Healthcare Hospital, Nanjing 210004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.fertnstert.2013.05.004","article-title":"The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure","volume":"100","author":"Blesa","year":"2013","journal-title":"Fertil. 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