Perfluorooctanoic acid induces cardiac dysfunction in human induced pluripotent stem cell-derived cardiomyocytes.

Perfluorooctanoic acid (PFOA), commonly found in drinking water, leads to widespread exposure through skin contact, inhalation, and ingestion, resulting in detectable levels of PFOA in the bloodstream. In this study, we found that exposure to PFOA disrupts cardiac function in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We observed reductions in field and action potentials in hiPSC-CMs exposed to PFOA. Furthermore, PFOA demonstrated a dose-dependent inhibitory effect on various ion channels, including the calcium, sodium, and potassium channels. Additionally, we noted dose-dependent inhibition of the expression of these ion channels in hiPSC-CMs following exposure to PFOA. These findings suggest that PFOA exposure can impair cardiac ion channel function and decrease the transcription of genes associated with these channels, potentially contributing to cardiac dysfunction such as arrhythmias. Our study sheds light on the electrophysiological and epigenetic consequences of PFOA-induced cardiac dysfunction, underscoring the importance of further research on the cardiovascular effects of perfluorinated compounds (PFCs).

Differential regulations of neural activity and survival in primary cortical neurons by PFOA or PFHpA.

Perfluorinated compounds (PFCs), organofluoride compounds comprising carbon-fluorine and carbon-carbon bonds, are used as water and oil repellents in textiles and pharmaceutical tablets; however, they are associated with potential neurotoxic effects. Moreover, the impact of PFCs on neuronal survival, activity, and regulation within the brain remains unclear. Additionally, the mechanisms through which PFCs induce neuronal toxicity are not well-understood because of the paucity of data. This study elucidates that perfluorooctanoic acid (PFOA) and perfluoroheptanoic acid (PFHpA) exert differential effects on the survival and activity of primary cortical neurons. Although PFOA triggers apoptosis in cortical neurons, PFHpA does not exhibit this effect. Instead, PFHpA modifies dendritic spine morphogenesis and synapse formation in primary cortical neuronal cultures, additionally enhancing neural activity and synaptic transmission. This research uncovers a novel mechanism through which PFCs (PFHpA and PFOA) cause distinct alterations in dendritic spine morphogenesis and synaptic activity, shedding light on the molecular basis for the atypical behaviors noted following PFC exposure. Understanding the distinct effects of PFHpA and PFOA could guide regulatory policies on PFC usage and inform clinical approaches to mitigate their neurotoxic effects, especially in vulnerable population.

Prenatal Di-methoxyethyl phthalate exposure impairs cortical neurogenesis and synaptic activity in the mice.

Di-methoxyethyl phthalate (DMEP) is a well-known environmentally prevalent endocrine disruptor and may be associated with neurodevelopmental disorders including attention deficit/hyperactivity disorder and intellectual disability. However, the regulatory mechanisms leading to these neurodevelopmental disorders are still poorly understood. Here, we demonstrate that prenatal DMEP exposure causes abnormal brain morphology and function in the mice. DMEP (50 mg/kg) was chronically administered to pregnant mice orally once a day starting on embryonic day 0 (E0) to breast-feeding cessation for the fetus. We found that prenatal DMEP exposure significantly reduced the number of neurons in the parietal cortex by impairing neurogenesis and gliogenesis during the developing cortex. Moreover, we found that prenatal DMEP exposure impaired dendritic spine architectures and synaptic activity in the parietal cortex. Finally, prenatal DMEP exposure in mice induces hyperactivity and reduces anxiety behaviors. Altogether, our study demonstrates that prenatal DMEP exposure leads to abnormal behaviors via impairment of neurogenesis and synaptic activity.

Cardiac toxicity from bisphenol A exposure in human-induced pluripotent stem cell-derived cardiomyocytes.

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical that is widely used in a variety of products, including plastics, medical equipment and receipts. Hence, most people are exposed to BPA through the skin, via inhalation and via the digestive system, and such exposure has been linked to cardiovascular diseases including coronary artery disease, hypertension, atherosclerosis, and myocardial infarction. However, the underlying mechanisms of cardiac dysfunction caused by BPA remain poorly understood. In this study, we found that BPA exposure altered cardiac function in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Acute BPA exposure in hiPSC-CMs resulted in reduced field potential, as measured by multielectrode array (MEA). Furthermore, we observed that BPA dose-dependently inhibited ICa, INa or IKr channels. In addition, BPA exposure dose-dependently inhibited calcium transients and contraction in hiPSC-CMs. Our findings suggest that BPA exposure leads to cardiac dysfunction and cardiac risk factors such as arrhythmia.