A comprehensive transcriptomic analysis of the bisphenol A affected kidney in mice

Marta Wiszpolska; Ewa Lepiarczyk; Łukasz Paukszto; Karol Gustaw Makowczenko; Aleksandra Lipka; Mateusz Artur Maździarz; Iwona Polak; Krystyna Makowska; Sławomir Gonkowski; Paulo Correia-de-Sá; Marta Majewska

doi:10.3389/fmolb.2023.1260716

A comprehensive transcriptomic analysis of the bisphenol A affected kidney in mice

Front Mol Biosci. 2023 Nov 24:10:1260716. doi: 10.3389/fmolb.2023.1260716. eCollection 2023.

Affiliations

¹ Department of Human Physiology and Pathophysiology, School of Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
² Department of Botany and Nature Protection, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
³ Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, Olsztyn, Poland.
⁴ Institute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
⁵ Department of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
⁶ Department of Clinical Diagnostics, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
⁷ Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
⁸ Laboratório de Farmacologia e Neurobiologia, Center for Drug Discovery and Innovative Medicines (MedInUP), Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal.

Abstract

Introduction: Bisphenol A (BPA) is a substance belonging to the endocrine-disrupting chemicals, globally used in the production of polycarbonate plastics. It has been found that BPA enhances carcinogenesis, triggers obesity and exerts a pathogenic effect in several disorders, such as type 2 diabetes, asthma, or increased blood pressure. Recent studies have revealed, that BPA has a harmful impact on the kidneys function, therefore, the current research aimed to explore the specific molecular changes triggered in these organs after oral BPA exposure in mice. Materials and Methods: The experiment was carried out on 12 (3-month-old) female mice. Six mice served as controls. The other 6 mice were treated with BPA in the drinking water at a dose of 50 mg/kg b. w. for 3 months. Then animals were euthanized, the kidneys were collected, and extracted RNA was used to perform RNA-seq. Results: Applied multistep bioinformatics revealed 433 differentially expressed genes (DEGs) in the BPA-treated kidneys (232 upregulated and 201 downregulated). Additionally, 95 differentially expressed long-noncoding RNAs (DELs) were revealed in BPA samples. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations indicated that BPA exposure resulted in profound changes in several essential processes, such as oxidative phosphorylation, mitochondrial and ribosome function, or chemical carcinogenesis. Conclusion: The obtained novel results suggest that BPA has a harmful impact on the fundamental processes of the kidney and significantly impairs its function by inducing mitochondrial dysfunction leading to oxidative stress and reactive oxygen species production.

Keywords: RNA-Seq; bisphenol A; kidney; mitochondrial dysfunction; oxidative stress.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Project financially supported by the statutory Fund of the School of Medicine, Collegium 597 Medicum (61.610.008–110), University of Warmia and Mazury in Olsztyn and National Science 598 Centre in Poland (Grant No. 2018/31/N/NZ7/01252). PC-d-S acknowledges the financial support from 599 the Portuguese Foundation for Science and Technology (FCT projects: UIDB/04308/2020 and 600 UIDP/04308/2020) via MedInUP.