Effects of Mono- (2-ethylhexyl) phthalate and Phthalic Acid Monobenzyl Ester on endometriosis using network toxicology, machine learning and molecular docking techniques.
Qi Wu, Yu Meng Sun, Qiong Hua Liu, Xing Yue Zhao, Ze Li, Li Xu, Wei Shi
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引用次数: 0
Abstract
Phthalate metabolites Mono- (2-ethylhexyl) phthalate(MEHP) and Phthalic Acid Monobenzyl Ester (MBZP) are widely present in the environment, can interfere with the endocrine system and accumulate in human tissues, and are closely related to the occurrence and development of endometriosis. In this study, by integrating multiple databases such as ChEMBL and STITCH, 503 human target genes of the two metabolites were screened out. After intersection with 1735 genes related to endometriosis, a core gene set of 50 was obtained. GO and KEGG enrichment analyses revealed that these genes were mainly involved in pathways such as arachidonic acid metabolism, IL-17 signaling pathway, cell burial, and complement-coagulation cascade reaction, and were involved in the processes of survival, migration, and fibrotic remodeling of ectopic endometrial cells driven by oxidative stress. Through the construction of PPI networks and the validation of machine learning models, ACE, MMP2, PPARG and SERPINE1 were identified as key hub proteins.The diagnostic ability AUC of each single gene reaches 0.80.Molecular docking experiments confirmed that MEHP and MBZP have high affinity (ΔG - 8.5 to - 6.3 kcal/mol) for the above-mentioned proteins, providing atomic-level evidence for their molecular regulatory mechanisms. This study systematically elucidated the multi-level mechanisms of endometriosis caused by phthalate exposure and proposed a precise diagnostic strategy based on core genes, providing new ideas for the prevention and targeted treatment of diseases related to environmental pollutants.
期刊介绍:
Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine.
All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.