Zhang Youtian, Wang Jian, Yang Hongchao, Guan Yong
Department of Urology, Tianjin Children's Hospital/Tianjin University Children's Hospital, Tianjin, China.
Department of Pediatric Surgery, Qilu Hospital of Shandong University Dezhou Hospital (Dezhou People's Hospital), Dezhou, Shandong, China.
Front Endocrinol (Lausanne). 2024 Dec 4;15:1490011. doi: 10.3389/fendo.2024.1490011. eCollection 2024.
Maternal exposure to environmental endocrine disruptors, such as phthalates, during pregnancy is a significant risk factor for the development of hypospadias. By consolidating existing research on the mechanisms by which phthalates induce hypospadias in rodent models, this systematic review aims to organize and analyze the discovered mechanisms and their potential connections.
The study involved all articles that explored the mechanisms of phthalate-induced hypospadias using rodent models. A comprehensive search of the PubMed and Web of Science databases was conducted using the terms "hypospadias" and "phthalates" before January 20, 2024. Then, two investigators screened for studies worthy of inclusion by setting inclusion and exclusion criteria.
Of the initial 326 search results, 22 were included in the subsequent analysis. Based on the commonalities among different results, the mechanisms of phthalate-induced hypospadias could be categorized into the following five groups: sex steroids-related signaling pathways (n=10), epithelial-mesenchymal transition (n=6), autophagy (n=5), apoptosis (n=4) and angiogenesis (n=2). Among these, sex steroids-related signaling pathways might serve as a central regulator among all mechanisms, and reactive oxygen species (ROS) also played an important mediating role.
The systematic review indicates that phthalates may initially disrupt the balance of sex steroids-related pathways, leading to abnormally elevated levels of ROS and subsequently to other functional abnormalities, ultimately resulting in the development of hypospadias. All these findings will help to improve prevention strategies during pregnancy to reduce the adverse effects of phthalates on the offspring.
孕期母亲暴露于环境内分泌干扰物（如邻苯二甲酸盐）是尿道下裂发生的一个重要风险因素。通过整合现有的关于邻苯二甲酸盐在啮齿动物模型中诱导尿道下裂机制的研究，本系统评价旨在整理和分析已发现的机制及其潜在联系。
该研究纳入了所有使用啮齿动物模型探索邻苯二甲酸盐诱导尿道下裂机制的文章。在2024年1月20日前，使用“尿道下裂”和“邻苯二甲酸盐”这两个术语对PubMed和Web of Science数据库进行了全面检索。然后，两名研究人员通过设定纳入和排除标准筛选出值得纳入的研究。
在最初的326条检索结果中，有22条被纳入后续分析。根据不同结果的共性，邻苯二甲酸盐诱导尿道下裂的机制可分为以下五组：性类固醇相关信号通路（n = 10）、上皮-间质转化（n = 6）、自噬（n = 5）、细胞凋亡（n = 4）和血管生成（n = 2）。其中，性类固醇相关信号通路可能是所有机制中的核心调节因子，活性氧（ROS）也发挥了重要的介导作用。
该系统评价表明，邻苯二甲酸盐可能最初破坏性类固醇相关通路的平衡，导致ROS水平异常升高，随后引发其他功能异常，最终导致尿道下裂的发生。所有这些发现将有助于改进孕期预防策略，以减少邻苯二甲酸盐对后代的不良影响。
