Antenatal Exposure to Plastic Pollutants: Study of the Bisphenols and Perfluoroalkyls Effects on Human Stem Cell Models

Abstract

Endocrine disruptors (EDs), such as Bisphenols (BPs) and Perfluoroalkyls (PFs), are a class of plastic pollutants widely used in industrial applications. Human exposure to these molecules usually occurs through ingestion of contaminated food and water. Once entered the human body they can interfere with endogenous hormone signaling, leading to a wide spectrum of diseases. It has been reported that BPs and PFs can cross the placental barrier accumulating in the fetal serum, but the detrimental consequences for human development remain to be clarified. Here we analyze the effects of different doses of bisphenol A and S (BPA, BPS) perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) on proliferation and mitochondrial health on different types of stem cells: through an integrated approach that combines data from pluripotent stem cells (hiPSCs) with that from the “environment” in which the embryo develops (fetal annexes-derived perinatal stem cells) we verified the potential developmental toxicity of the in utero EDs exposure. Data obtained showed that overall, BPs, and PFs tended to increase the proliferation rate of perinatal stem cells; a similar response was observed in hiPSCs exposed to very low doses of BPs and PFs, while at higher concentrations these chemicals were toxic; in addition, both the BPs and the PFs exerted a mitotoxic effects hiPSCs at all the concentration studied. All these data suggest that antenatal exposure to BPs and PFs, also at very low concentrations, may modify the biological characteristics of stem cells present in both the developing fetus and the fetal annexes, thus perturbing normal human development.

Machine learning identifies phenotypic profile alterations of human dopaminergic neurons exposed to bisphenols and perfluoroalkyls

“…Although association studies already suggested a relationship between the exposure to EDs and PD development, our results provide the first evidence of the threatening action of BPs and PFs on a human mDAN model, showing the neuronal biological features affected by EDs exposure. In line with previous data obtained in other neuronal or stem cell models [30][31][32], in our setting BPs and PFs did not impact cell viability. However, high content imaging analysis showed that 72-hour exposure to BPA, BPS, or PFOA determined an increase of αSyn levels in human mDANs and this effect was particularly evident at the highest concentration tested (2 µM) (Figure 2D, Figure 3B, Figure 6B).…”

The Effects of Combined Exposure to Bisphenols and Perfluoroalkyls on Human Perinatal Stem Cells and the Potential Implications for Health Outcomes

“…Furthermore, PFs have been shown to interfere with thyroid, androgenic, and estrogenic pathways in pregnancy, affecting placental morphology and fetal survival and growth [27][28][29][30]. We already described the sensibility of the diverse human stem cells to different doses of BPs and PFs [31,32]. In this study, the toxic effects of BPs and PFs, alone or in combination, were tested in hAFSCs and hFM-MSCs by evaluating cell proliferation, mitochondrial response, and the expression of genes pivotal for stem cell biology.…”

Machine learning identifies phenotypic profile alterations of human dopaminergic neurons exposed to bisphenols and perfluoroalkyls

“…Liao et al investigated the effect of different PFs on cultured rat hippocampal neurons and demonstrated that PFOS and PFOA decreased neurite length by about 25% and 20%, respectively 51 . It is also known that BPs and PFs, interfering with the endocrine system, do not show a linear dose–response effect 36 , 37 . In our study we found that some investigated features were altered at low (0.1 µM) and high concentration (2 µM), but not at medium ones (1 µM).…”