Platform to study intracellular polystyrene nanoplastic pollution and clinical outcomes

Author:

Bojic Sanja12,Falco Matias M.34,Stojkovic Petra5,Ljujic Biljana2,Gazdic Jankovic Marina2,Armstrong Lyle1ORCID,Markovic Nebojsa5,Dopazo Joaquin346,Lako Majlinda1ORCID,Bauer Roman1,Stojkovic Miodrag52ORCID

Affiliation:

1. Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK

2. Faculty of Medical Sciences, Human Genetics, University of Kragujevac, Serbia

3. Clinical Bioinformatics Area, Fundación Progreso y Salud (FPS), Hospital Virgen del Rocío, Seville, Spain

4. Bioinformatics in Rare Diseases (BiER), Centro de Investigaciones Biomédicas en Red en Enfermedades Raras (CIBERER), Seville, Spain

5. SPEBO Medical Fertility Hospital, Leskovac, Serbia

6. Computational Systems Medicine group, Institute of Biomedicine of Seville (IBIS) Hospital Virgen del Rocío, Seville, Spain

Abstract

Abstract 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.

Funder

Serbian Ministry of Education, Science and Technology

European Regional Development Funds

Spanish Ministry of Economy and Competitiveness

Engineering and Physical Sciences Research Council of the United Kingdom

ERC consolidator

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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