{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:24:14Z","timestamp":1791563054134,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003851","name":"Education Department of Heilongjiang","doi-asserted-by":"publisher","award":["LH2024H044"],"award-info":[{"award-number":["LH2024H044"]}],"id":[{"id":"10.13039\/501100003851","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Science Foundation of China Youth Fund","award":["82405036"],"award-info":[{"award-number":["82405036"]}]},{"name":"The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University","award":["JBGS-FAMP202304"],"award-info":[{"award-number":["JBGS-FAMP202304"]}]},{"name":"Science and Technology Fund Project of Guizhou Provincial Health Commission","award":["gzwkj2024-516"],"award-info":[{"award-number":["gzwkj2024-516"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Infertility is a prevalent clinical issue which disrupts normal human life and exerts an impact on fertility rates within the population. The increase in environmental pollutants, including acetyl tributyl citrate (ATBC), has given rise to concerns regarding their potential toxicity in infertility-related disorders. Icariin exhibits therapeutic effects on infertility, yet its mechanism of action against plasticiser-induced reproductive disorders remains unclear. This study aims to elucidate the potential toxicological targets and molecular mechanisms of ATBC-induced infertility, as well as the therapeutic targets and mechanisms of icariin in treating ATBC-induced reproductive disorders, through network toxicology, molecular-docking techniques and molecular dynamics simulation. Utilising the component-target database SwissTargetPrediction, the Similarity Ensemble Approach, PharmMapper, the ChEMBL database, and disease databases including the Therapeutic Target Database, OMIM, GeneCards, and DrugBank, 63 targets for ATBC-induced infertility and 33 targets for icariin treatment were identified. Screening via the STRING platform and Cytoscape 3.10.1 software yielded four core targets for ATBC-induced infertility\u2014HSP90AA1, PIK3CA, CASP3, HRAS\u2014and four core targets for icariin treatment\u2014IL6, TNF, STAT3, and INS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that ATBC-induced infertility correlates with pathways including pathways in cancer, prostate cancer, and PI3K-Akt signalling pathways. Conversely, the core targets of icariin therapy for related reproductive disorders are closely associated with tumour-associated signalling pathways and the AGE-RAGE signalling pathway. Molecular-docking and molecular dynamics simulation further confirmed the strong binding interactions between ATBC and infertility-related targets, as well as between icariin and core targets for treating reproductive disorders. This provides a theoretical foundation for understanding ATBC\u2019s toxicological targets and the complex molecular mechanisms underpinning icariin\u2019s treatment of infertility. It informs the development of strategies for icariin to prevent and treat infertility caused by exposure to ATBC-containing plastics or excessive ATBC contact.<\/jats:p>","DOI":"10.3390\/ijms27062918","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T08:02:49Z","timestamp":1774339369000},"page":"2918","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Study on the Mechanism of Acetyl Tributyl Citrate-Induced Infertility Toxicity and the Protective Action of Icariin Based on Network Toxicology, Network Pharmacology, Molecular-Docking Technology and Molecular Dynamics Simulation"],"prefix":"10.3390","volume":"27","author":[{"given":"Xiaowei","family":"Sun","sequence":"first","affiliation":[{"name":"College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang 157011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang 157011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxing","family":"Han","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang 157011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Du","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang 157011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang 157011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Miu","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang 157011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang 157011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobo","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, School of Pharmaceutical Sciences, Guizhou Medical University, Guian New District, Guiyang 550025, China"},{"name":"The High Efficacy Application of Characteristic Natural Medicinal Resources Engineering Research Center of Guizhou Province, School of Pharmacy, Guizhou Medical University, Guiyang 550025, China"},{"name":"Guizhou International Science & Technology Cooperation Base for Natural Drugability Research (Joint Laboratory), School of Pharmacy, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0669-0530","authenticated-orcid":false,"given":"Chunlei","family":"Wan","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang 157011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1093\/humrep\/dem046","article-title":"International estimates of infertility prevalence and treatment-seeking: Potential need and demand for infertility medical care","volume":"22","author":"Boivin","year":"2007","journal-title":"Hum. 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