Yuqi Li, Juan Wang, Zhiyu Liu, Xinyao Zhu, Qilong Wu, Chunyang Meng, Qingfu Deng
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引用次数: 0
Abstract
Background: In recent years, phthalate plasticizers have been increasingly linked to various male reproductive health issues. However, their relationship with erectile dysfunction (ED) remains insufficiently studied. This study aims to elucidate the molecular mechanisms by which phthalate plasticizers contribute to ED.
Methods: Using a network toxicology approach, we predicted potential molecular targets of three common phthalates-DEHP, DIBP, and DMP-associated with ED through multiple online databases. Next, we integrated transcriptomic datasets from three established ED rat models (diabetic, neurogenic, and hypertensive) to identify more robust and representative candidate genes. Subsequently, LASSO and SVM-RFE machine learning algorithms were employed to screen for key phthalate related ED genes. Molecular docking was then conducted to validate the binding affinity between phthalates and these candidate targets.
Results: Network toxicology analysis identified 101 genes potentially linking phthalates to ED. Enrichment analyses revealed that these genes are primarily involved in endothelial dysfunction, oxidative stress, and cell growth regulation. From the integrated ED transcriptomic dataset, 1002 differentially expressed genes were identified, among which 12 overlapped with the phthalate-ED associated genes. These overlapping genes were closely related to neurodegenerative diseases and metabolic disorders. LASSO and SVM-RFE models further narrowed the list to four key genes: CDKN1B, IDH1, CASR, and PRNP.
Conclusion: The four key genes-CDKN1B, IDH1, CASR, and PRNP-appear to play critical roles in phthalate-induced ED. These genes are potentially involved in mechanisms such as oxidative stress dysregulation, neural injury, and endocrine disorders. Our findings provide important theoretical insights into the pathogenesis and prevention of environmentally induced ED.
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.