Cell-free circulating epigenomic signatures: Non-invasive biomarkers of pregnancy-related outcomes associated with plasticizer exposure

Globally, plastics have revolutionized industrial and societal advancements, but their durability and low degradability have led to significant environmental pollution. Plasticizers, such as bisphenol A (BPA) and phthalates, are widely used to enhance the flexibility and durability of plastics; however, they are also recognized as endocrine-disrupting chemicals (EDCs) with severe health implications. These chemicals are associated with reproductive toxicity, developmental disruptions, and multigenerational health effects. Recent research has highlighted the impact of plasticizers on irreversible epigenetic modifications, which influence abnormal gene expression patterns without altering the DNA sequence. Histone alterations, DNA methylation, and non-coding RNA regulation are essential pathways. Exposure to BPA and phthalates disrupts these epigenetic processes, leading to long-term reproductive health issues, including infertility, implantation failures, preterm birth, and pregnancy complications such as gestational diabetes and preeclampsia. Cell-free circulating nucleic acids are promising non-invasive biomarkers for the early detection of pregnancy complications, such as preeclampsia, with the potential to predict sensitivity and track gestational age and underlying pathophysiological processes. Combining circulating nucleic acid analysis with evaluations of plasticizer exposure may aid in stratifying high-risk pregnancies. Here, we examined the mechanisms by which plasticizers induce epigenetic alterations, their impact on reproductive health and pregnancy outcomes, and potential biomarkers for identifying these changes to facilitate tailored management of pregnancy complications and assess reproductive health risks.