Bisphenol TMC disturbs mitochondrial activity and biogenesis, reducing lifespan and healthspan in the nematode Caenorhabditis elegans

Abstract

Rising concerns about Bisphenol A (BPA) toxicity have prompted the search for safer alternatives. However, concerns persist regarding the safety of replacements like bisphenol TMC (BPTMC), a rapidly emerging BPA substitute. Utilizing the in vivo model organism Caenorhabditis elegans (C. elegans), whose shared genes mirror human biology, we aim to unveil the potential toxicity of BPTMC on a live animal. C. elegans exposed to 1 mM BPTMC exhibited developmental delays, reduced reproduction, and diminished longevity. Furthermore, investigation across multiple developmental stages of C. elegans revealed increased mortality, heightened oxidative stress, and impaired thermal stress resistance. Notably, exposure to BPTMC resulted in mitochondrial unfolded protein response (mitoUPR) and abnormalities, including reduced oxygen consumption and lowered mitochondrial membrane potential. Additionally, BPTMC increased reactive oxygen species levels but decreased mitochondrial population. Transcriptome analysis revealed that BPTMC induces alterations in the expression of genes associated with mitochondrial biogenesis. Our findings raise crucial concerns about BPTMC as a safe BPA alternative. The observed widespread toxicity across key life stages suggests a need for further investigation into the potential toxicity of BPTMC on human health and environmental consequences.