{"title":"基于网络毒理学和分子对接研究DBP和DEHP在PCOS发展中的作用机制。","authors":"Kang Yi-Fan, Liu Jian-Rong","doi":"10.1007/s00210-025-04173-0","DOIUrl":null,"url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) constitutes a prevalent endocrine disorder among females, exhibiting a significant incidence rate. The etiology of PCOS predominantly attributes to environmental determinants. Phthalate esters, including dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), have been demonstrated to exert detrimental effects on reproductive function. However, the effects of these plasticizers on female reproductive health have not been clearly investigated. In the present investigation, we employed network toxicological methodologies to delineate the pivotal genes and associated pathways that are implicated in the pathogenesis of PCOS induced by DBP and DEHP. Molecular docking methodologies were employed to ascertain the interaction between the investigational compound and the designated target protein. The present study delineates pivotal targets, namely AKT1, SRC, PIK3R1, EGFR, ESR1, and STAT3, which are instrumental in the mediation of PCOS. The genes predominantly participate in the EGFR pathway, insulin signaling pathway, and oocyte damage, significantly compromising female ovarian functionality. This investigation underscores the integration of network toxicology, molecular docking, and cell experiment methodologies to elucidate the toxicological properties and underlying molecular mechanisms of plasticizers in the context of PCOS. This study provides a prospective therapeutic target to mitigate the harmful effects of plasticizers on female reproductive health.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"14239-14255"},"PeriodicalIF":3.1000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Research mechanism of DBP and DEHP in the development of PCOS based on network toxicology and molecular docking.\",\"authors\":\"Kang Yi-Fan, Liu Jian-Rong\",\"doi\":\"10.1007/s00210-025-04173-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Polycystic ovary syndrome (PCOS) constitutes a prevalent endocrine disorder among females, exhibiting a significant incidence rate. The etiology of PCOS predominantly attributes to environmental determinants. Phthalate esters, including dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), have been demonstrated to exert detrimental effects on reproductive function. However, the effects of these plasticizers on female reproductive health have not been clearly investigated. In the present investigation, we employed network toxicological methodologies to delineate the pivotal genes and associated pathways that are implicated in the pathogenesis of PCOS induced by DBP and DEHP. Molecular docking methodologies were employed to ascertain the interaction between the investigational compound and the designated target protein. The present study delineates pivotal targets, namely AKT1, SRC, PIK3R1, EGFR, ESR1, and STAT3, which are instrumental in the mediation of PCOS. The genes predominantly participate in the EGFR pathway, insulin signaling pathway, and oocyte damage, significantly compromising female ovarian functionality. This investigation underscores the integration of network toxicology, molecular docking, and cell experiment methodologies to elucidate the toxicological properties and underlying molecular mechanisms of plasticizers in the context of PCOS. This study provides a prospective therapeutic target to mitigate the harmful effects of plasticizers on female reproductive health.</p>\",\"PeriodicalId\":18876,\"journal\":{\"name\":\"Naunyn-Schmiedeberg's archives of pharmacology\",\"volume\":\" \",\"pages\":\"14239-14255\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Naunyn-Schmiedeberg's archives of pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00210-025-04173-0\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/25 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Naunyn-Schmiedeberg's archives of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00210-025-04173-0","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/25 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Research mechanism of DBP and DEHP in the development of PCOS based on network toxicology and molecular docking.
Polycystic ovary syndrome (PCOS) constitutes a prevalent endocrine disorder among females, exhibiting a significant incidence rate. The etiology of PCOS predominantly attributes to environmental determinants. Phthalate esters, including dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), have been demonstrated to exert detrimental effects on reproductive function. However, the effects of these plasticizers on female reproductive health have not been clearly investigated. In the present investigation, we employed network toxicological methodologies to delineate the pivotal genes and associated pathways that are implicated in the pathogenesis of PCOS induced by DBP and DEHP. Molecular docking methodologies were employed to ascertain the interaction between the investigational compound and the designated target protein. The present study delineates pivotal targets, namely AKT1, SRC, PIK3R1, EGFR, ESR1, and STAT3, which are instrumental in the mediation of PCOS. The genes predominantly participate in the EGFR pathway, insulin signaling pathway, and oocyte damage, significantly compromising female ovarian functionality. This investigation underscores the integration of network toxicology, molecular docking, and cell experiment methodologies to elucidate the toxicological properties and underlying molecular mechanisms of plasticizers in the context of PCOS. This study provides a prospective therapeutic target to mitigate the harmful effects of plasticizers on female reproductive health.
期刊介绍:
Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.