Bisphenol A Disrupts Mitochondrial Functionality Leading to Senescence and Apoptosis in Human Amniotic Mesenchymal Stromal Cells

Abstract

AbstractIn today’s context, microplastics pollution has become an increasingly pressing issue not only for the environmental fallout but also for the assumed negative effects on human health. It is now well-established that microplastics (>1 mm in size) can enter the human body through ingestion, inhalation, dermal contact and also maternal-fetal transmission. Alarming was the recent findings of microplastics within the human term placenta. Among the degradation by-products of microplastics, Bisphenol A (BPA) has emerged as a hazardous chemical, with potential toxicity at multisystemic level, particularly on the earliest stages of human development. Based on these findings, our study focuses on assessing the impact of BPA on properties and functions of mesenchymal stromal cells isolated from the amniotic membrane (hAMSC) of the human term placenta. The amniotic membrane surrounds the fetus, playing a fundamental protective role toward toxic chemicals and pollutants that the mother may encounter. Our research revealed how exposure to increasing concentrations of BPA compromise mitochondrial functionality in hAMSC, resulting in enhanced production of reactive oxygen species at mitochondrial level (mtROS). This, in turn, leads to the stabilization of p53, which triggers an increased expression of p21 and p27 encoding genes and an imbalance in the genetic expression of Bax and Bcl-2. Additionally, we observed upregulated expression of cytokines and chemokines associated with the senescence-associated secretory phenotype (SASP). The increased oxidative stress, which plays a central role in BPA-mediated toxicity, can trigger the activation of the senescence pathways, or culminate in cell death, due to the overwhelming stress conditions. Therefore, our results provide novel insights into the mechanism of action of BPA and elucidates its impact on the functionality of hAMSC. This underscores the pressing need to reconsider the use of BPA as a plastic additive, mitigating the potential adverse effects on babies.