Computational and Theoretical Approach to Deciphering Potential PFAS-Induced Toxicity on the Human Estrogen and Sperm Receptors, with Implications on Female Fertility

Abstract

Despite warnings from researchers, the use of per- and polyfluoroalkyl substances (PFAS) in consumer products continues to rise, significantly increasing their presence in the environment and human bodies. The cautionary advice has not yet led to meaningful action and the problem persists. This study utilized computer-based simulations to investigate the potential harmful effects of PFAS on human fertility, specifically their impact on female fertility by binding to the human estrogen and sperm receptors, highlighting a possible toxic mechanism. Molecular docking simulations revealed that perfluorotetradecanoic acid (PFTeDA), perfluorotridecanoic acid (PFTriA), perfluorodecanesulfonic acid (PFDS), and perfluorododecanoic acid (PFDoA) exhibited high binding affinity on both protein targets, with binding affinities comparable to or exceeding those of the native ligand. PFTeDA demonstrated the highest binding affinity among the studied PFAS on both proteins. Molecular dynamics simulations confirmed the stability of PFTeDA binding at both targets, suggesting persistence at these biological sites. Density functional theory analysis revealed that PFDS and PFDoA possess high reactivity, indicating a propensity for interaction with fertility proteins. These findings suggest that these PFAS may pose significant toxicity to female fertility proteins, potentially leading to reproductive issues. Further research is imperative to elucidate the underlying mechanisms and to develop effective countermeasures against the potentially deleterious effects of these PFAS on human reproductive health, thereby informing evidence-based strategies for mitigating this critical threat to human fertility and reproductive well-being. Received: 11 November 2024 | Revised: 14 January 2025 | Accepted: 11 February 2025 Conflicts of Interest The authors declare that they have no conflicts of interest to this work. Data Availability Statement The data that support this work are available upon reasonable request to the corresponding author. Author Contribution Statement Maryjane Ada Nnabuchi: Validation, Formal analysis, Investigation, Resources, Data curation, Writing – original draft. Chidi Edbert Duru: Conceptualization, Methodology, Software, Resources, Writing – review & editing, Visualization, Supervision, Project administration.