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SYSTEMATIC REVIEW article

Front. Endocrinol.
Sec. Developmental Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1490011

The Potential Mechanisms Underlying Phthalate-Induced Hypospadias: A Systematic Review of Rodent Model Studies

Provisionally accepted
Youtian Zhang Youtian Zhang 1Jian Wang Jian Wang 1Hongchao Yang Hongchao Yang 2Yong Guan Yong Guan 1*
  • 1 Tianjin Children's Hospital, Tianjin, China
  • 2 Dezhou City People’s Hospital, Dezhou, Shandong Province, China

The final, formatted version of the article will be published soon.

    Objectives: 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.Results: 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), epithelialmesenchymal 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

    Keywords: phthalates, Hypospadias, Molecular mechanisms, sex steroids, ROS

    Received: 02 Sep 2024; Accepted: 18 Nov 2024.

    Copyright: © 2024 Zhang, Wang, Yang and Guan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yong Guan, Tianjin Children's Hospital, Tianjin, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.