Exploring the mechanism of plastic additives on reproductive disorders based on network toxicology and molecular

Aiqin Lian1, Wenwei Zheng2, Yi Ran Liu3,4

  • 1Department of Reproductive Clinic, Quanzhou Hospital of Traditional Chinese Medicine, Quanzhou, Fujian Province, China.

Insights

Phthalate esters (PAEs) and organophosphate esters (OPEs) are linked to female reproductive disorders. This study identifies key molecular targets and biomarkers for conditions like PCOS, RPL, and endometriosis.

Area of Science:

  • Toxicology
  • Molecular Biology
  • Genomics

Background:

  • Phthalate esters (PAEs) and organophosphate esters (OPEs) are widespread environmental pollutants with endocrine-disrupting effects.
  • Growing evidence suggests a link between PAE/OPE exposure and female reproductive disorders, but specific molecular targets and shared mechanisms remain unclear.
  • Polycystic ovary syndrome (PCOS), recurrent pregnancy loss (RPL), and endometriosis are clinically related conditions potentially impacted by these exposures.

Purpose of the Study:

  • To systematically investigate the molecular interactions between PAEs/OPEs and their targets across PCOS, RPL, and endometriosis.
  • To identify disease-specific and shared molecular targets and pathogenic pathways.
  • To explore the potential of identified targets as biomarkers for risk stratification.

Main Methods:

  • Utilized an integrative network toxicology framework.
  • Combined molecular docking, network pharmacology, and multi-omics analysis.
  • Analyzed PAE/OPE-target interactions across the three reproductive disorders.

Main Results:

  • Identified disease-specific hub genes: ESR1 and MMP9 for PCOS, CTNNB1 and BCL2 for RPL, IL6 and NFKB1 for endometriosis.
  • Revealed shared pathogenic mechanisms including NF-κB activation, PI3K-AKT dysregulation, and microRNA-mediated regulation.
  • Confirmed direct binding of specific PAEs/OPEs to key targets via molecular docking.
  • Developed diagnostic nomograms with high AUCs (0.72-0.94) for risk stratification.

Conclusions:

  • Established a cross-disease network framework connecting PAE/OPE exposure to female reproductive toxicity.
  • Provided mechanistic insights into the molecular pathogenesis of PCOS, RPL, and endometriosis.
  • Highlighted potential candidate biomarkers for risk assessment and targeted prevention strategies.

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