Understanding the role of endocrine disrupting chemicals in testicular germ cell cancer: Insights into molecular mechanisms

Mol Aspects Med. 2024 Oct:99:101307. doi: 10.1016/j.mam.2024.101307. Epub 2024 Aug 29.

Abstract

This comprehensive review examines the complex interplay between endocrine disrupting chemicals (EDCs) and the development of testicular germ cell tumors (TGCTs). Despite the high cure rates of TGCTs, challenges in diagnosis and treatment remain, necessitating a deeper understanding of the etiology of the disease. Here, we emphasize current knowledge on the role of EDCs as potential risk factors for TGCTs, focusing on pesticides and perfluorinated and polyfluoroalkyl substances (PFAs/PFCs). Evidence suggests that EDCs disrupt endocrine pathways and induce epigenetic changes that contribute to the development of TGCTs. However, the direct link between EDCs and TGCTs remains elusive and requires further investigation of the molecular mechanisms. We also highlighted the importance of studying nuclear receptors as potential targets for understanding TGCT etiology. In addition, recent evidence implicates PFAs/PFCs in TGCT incidence, highlighting the need for further research into their impact on human health. Overall, this review provides valuable insights into the potential role of EDCs in TGCT development and suggests avenues for future research, while also highlighting how understanding their influence may pave the way for novel therapeutic approaches to improve disease management.

Keywords: Chemoresistance; Epigenetics; PFAs/PFCs; Pesticides; Testicular germ cell tumor.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endocrine Disruptors* / adverse effects
  • Environmental Exposure / adverse effects
  • Epigenesis, Genetic
  • Fluorocarbons
  • Humans
  • Male
  • Neoplasms, Germ Cell and Embryonal* / drug therapy
  • Neoplasms, Germ Cell and Embryonal* / etiology
  • Neoplasms, Germ Cell and Embryonal* / genetics
  • Neoplasms, Germ Cell and Embryonal* / metabolism
  • Neoplasms, Germ Cell and Embryonal* / pathology
  • Pesticides / adverse effects
  • Risk Factors
  • Testicular Neoplasms* / drug therapy
  • Testicular Neoplasms* / etiology
  • Testicular Neoplasms* / genetics
  • Testicular Neoplasms* / metabolism

Substances

  • Endocrine Disruptors
  • Pesticides
  • Fluorocarbons

Supplementary concepts

  • Testicular Germ Cell Tumor