Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells

• Published in: Toxins 2023-02, Vol.15 (2), p.140
• Main Authors: Márton, Éva, Varga, Alexandra, Penyige, András, Birkó, Zsuzsanna, Balogh, István, Nagy, Bálint, Szilágyi, Melinda
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Bisphenol A; Cell growth; Cell migration; Cell proliferation; Comparative analysis; Estrogens; Female; Gene expression; Gene sequencing; Gene set enrichment analysis; Genes; Genetic aspects; Genetic transcription; Gynecology; Health aspects; Hormone replacement therapy; Humans; Infertility; Kinases; Ligands; Messenger RNA; Metabolism; MicroRNA; MicroRNAs; MicroRNAs - metabolism; miRNA; mycotoxin; Mycotoxins; Ovarian cancer; Ovaries; Physiological aspects; Physiological effects; Physiology; Properties; Ribonucleic acid; RNA; RNA, Messenger - genetics; Sex hormones; Transcription factors; Transcriptome; Transcriptomics; xenoestrogen; Xenoestrogens; Zearalenone
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins15020140

Xenoestrogens are natural or synthetic compounds that mimic the effect of endogenous estrogens and might cause cancer. We aimed to compare the global transcriptomic response to zearalenone (ZEA; mycotoxin) and bisphenol A (BPA; plastic additive) with the effect of physiological estradiol (E2) in the PEO1 human ovarian cell line by mRNA and microRNA sequencing. Estrogen exposure induced remarkable transcriptomic changes: 308, 288 and 63 genes were upregulated (log FC > 1); 292, 260 and 45 genes were downregulated (log FC < -1) in response to E2 (10 nM), ZEA (10 nM) and BPA (100 nM), respectively. Furthermore, the expression of 13, 11 and 10 miRNAs changed significantly (log FC > 1, or log FC < -1) after exposure to E2, ZEA and BPA, respectively. Functional enrichment analysis of the significantly differentially expressed genes and miRNAs revealed several pathways related to the regulation of cell proliferation and migration. The effect of E2 and ZEA was highly comparable: 407 genes were coregulated by these molecules. We could identify 83 genes that were regulated by all three treatments that might have a significant role in the estrogen response of ovarian cells. Furthermore, the downregulation of several miRNAs (miR-501-5p, let-7a-2-3p, miR-26a-2-3p, miR-197-5p and miR-582-3p) was confirmed by qPCR, which might support the proliferative effect of estrogens in ovarian cells.