Platform to study intracellular polystyrene nanoplastic pollution and clinical outcomes

• Published in: Stem cells (Dayton, Ohio) Ohio), 2020-10, Vol.38 (10), p.1321-1325
• Main Authors: Bojic, Sanja, Falco, Matias M., Stojkovic, Petra, Ljujic, Biljana, Gazdic Jankovic, Marina, Armstrong, Lyle, Markovic, Nebojsa, Dopazo, Joaquin, Lako, Majlinda, Bauer, Roman, Stojkovic, Miodrag
• Format: Article
• Language: English
• Subjects: Beverages; Cardiovascular diseases; Circuits; Clinical outcomes; embryo; Embryos; Environmental health; Extracellular matrix; Gene set enrichment analysis; Growth factors; Health risks; Heart diseases; Heart valves; induced pluripotent stem cells; Intracellular; Ischemia; Microplastics; Plastic pollution; Pluripotency; Pollution; Polymers; Polystyrene; Polystyrene resins; Stem cells; toxicity; Transcription; transcription factors; Transforming growth factor-b
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.3244

Increased pollution by plastics has become a serious global environmental problem, but the concerns for human health have been raised after reported presence of microplastics (MPs) and nanoplastics (NPs) in food and beverages. Unfortunately, few studies have investigate the potentially harmful effects of MPs/NPs on early human development and human health. Therefore, we used a new platform to study possible effects of polystyrene NPs (PSNPs) on the transcription profile of preimplantation human embryos and human induced pluripotent stem cells (hiPSCs). Two pluripotency genes, LEFTY1 and LEFTY2, which encode secreted ligands of the transforming growth factor‐beta, were downregulated, while CA4 and OCLM, which are related to eye development, were upregulated in both samples. The gene set enrichment analysis showed that the development of atrioventricular heart valves and the dysfunction of cellular components, including extracellular matrix, were significantly affected after exposure of hiPSCs to PSNPs. Finally, using the HiPathia method, which uncovers disease mechanisms and predicts clinical outcomes, we determined the APOC3 circuit, which is responsible for increased risk for ischemic cardiovascular disease. These results clearly demonstrate that better understanding of NPs bioactivities and its implications for human health is of extreme importance. Thus, the presented platform opens further aspects to study interactions between different environmental and intracellular pollutions with the aim to decipher the mechanism and origin of human diseases. Schematic illustration of the platform and experimental design with 40 nm polystyrene nanoplastics. Human blastocysts and human induced pluripotent stem cells were exposed for 24 hours to polystyrene nanoitems and used for whole transcriptome sequencing and in depth RNA analysis through Next‐Generation Sequencing technology. In preprocessment, gene IDs were translated, scaled, normalized, and used for signaling pathways, analysis, and delivery of the report.