Impact of 17-alpha ethinyl estradiol (EE2) and diethyl phthalate (DEP) exposure on microRNAs expression and their target genes in differentiated SH-SY5Y cells
Abstract Environmental endocrine disruptor chemicals (EDCs) have raised significant concerns due to their potential adverse effects on human health, particularly on the central nervous system (CNS). This study provides a comparative analysis of the effects of 17-alpha ethinyl estradiol (EE2) and die...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-86911-1 |
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| author | Agnese Graziosi Camilla Corrieri Giulia Sita Luca Ghelli Sabrina Angelini Roberta d’Emmanuele di Villa Bianca Emma Mitidieri Raffaella Sorrentino Patrizia Hrelia Fabiana Morroni |
| author_facet | Agnese Graziosi Camilla Corrieri Giulia Sita Luca Ghelli Sabrina Angelini Roberta d’Emmanuele di Villa Bianca Emma Mitidieri Raffaella Sorrentino Patrizia Hrelia Fabiana Morroni |
| author_sort | Agnese Graziosi |
| collection | DOAJ |
| description | Abstract Environmental endocrine disruptor chemicals (EDCs) have raised significant concerns due to their potential adverse effects on human health, particularly on the central nervous system (CNS). This study provides a comparative analysis of the effects of 17-alpha ethinyl estradiol (EE2) and diethyl phthalate (DEP) on neuronal cell proliferation and neurotoxicity. Using differentiated SH-SY5Y human neuronal cells, we evaluated cell viability, microRNA (miRNA) regulation, and RNA expression following exposure to subtoxic concentrations of EE2 and DEP. Our results show that both EDCs downregulated specific miRNAs—miR-18b-5p, miR-200a-3p, and miR-653-5p—affecting key processes such as cell proliferation, survival, and apoptosis. Gene expression analysis revealed the upregulation of EGFR, IGF1R, BTG2, and SH3BP4, implicating these miRNAs in the regulation of the Ras and PI3K/Akt/mTOR pathways. Our findings highlight distinct cellular responses: DEP disrupts PTEN activity, while EE2 enhances phosphorylation within the PI3K/Akt/mTOR pathway, promoting pro-survival and anti-apoptotic signals. This study emphasizes the urgent need for regulatory measures to mitigate the neurotoxic effects of EDCs and offers valuable insights into their molecular impacts on brain health. |
| format | Article |
| id | doaj-art-7a9e60aa7a904129a42fb1684bf7713b |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-7a9e60aa7a904129a42fb1684bf7713b2025-01-26T12:26:11ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-86911-1Impact of 17-alpha ethinyl estradiol (EE2) and diethyl phthalate (DEP) exposure on microRNAs expression and their target genes in differentiated SH-SY5Y cellsAgnese Graziosi0Camilla Corrieri1Giulia Sita2Luca Ghelli3Sabrina Angelini4Roberta d’Emmanuele di Villa Bianca5Emma Mitidieri6Raffaella Sorrentino7Patrizia Hrelia8Fabiana Morroni9Department of Pharmacy and BioTechnology – FaBiT, Alma Mater Studiorum – University of BolognaDepartment of Pharmacy and BioTechnology – FaBiT, Alma Mater Studiorum – University of BolognaDepartment of Pharmacy and BioTechnology – FaBiT, Alma Mater Studiorum – University of BolognaDepartment of Pharmacy and BioTechnology – FaBiT, Alma Mater Studiorum – University of BolognaDepartment of Pharmacy and BioTechnology – FaBiT, Alma Mater Studiorum – University of BolognaDepartment of Pharmacy, School of Medicine and Surgery, University of Study of Naples – Federico IIDepartment of Pharmacy, School of Medicine and Surgery, University of Study of Naples – Federico IIDepartment of Pharmacy, School of Medicine and Surgery, University of Study of Naples – Federico IIDepartment of Pharmacy and BioTechnology – FaBiT, Alma Mater Studiorum – University of BolognaDepartment of Pharmacy and BioTechnology – FaBiT, Alma Mater Studiorum – University of BolognaAbstract Environmental endocrine disruptor chemicals (EDCs) have raised significant concerns due to their potential adverse effects on human health, particularly on the central nervous system (CNS). This study provides a comparative analysis of the effects of 17-alpha ethinyl estradiol (EE2) and diethyl phthalate (DEP) on neuronal cell proliferation and neurotoxicity. Using differentiated SH-SY5Y human neuronal cells, we evaluated cell viability, microRNA (miRNA) regulation, and RNA expression following exposure to subtoxic concentrations of EE2 and DEP. Our results show that both EDCs downregulated specific miRNAs—miR-18b-5p, miR-200a-3p, and miR-653-5p—affecting key processes such as cell proliferation, survival, and apoptosis. Gene expression analysis revealed the upregulation of EGFR, IGF1R, BTG2, and SH3BP4, implicating these miRNAs in the regulation of the Ras and PI3K/Akt/mTOR pathways. Our findings highlight distinct cellular responses: DEP disrupts PTEN activity, while EE2 enhances phosphorylation within the PI3K/Akt/mTOR pathway, promoting pro-survival and anti-apoptotic signals. This study emphasizes the urgent need for regulatory measures to mitigate the neurotoxic effects of EDCs and offers valuable insights into their molecular impacts on brain health.https://doi.org/10.1038/s41598-025-86911-1 |
| spellingShingle | Agnese Graziosi Camilla Corrieri Giulia Sita Luca Ghelli Sabrina Angelini Roberta d’Emmanuele di Villa Bianca Emma Mitidieri Raffaella Sorrentino Patrizia Hrelia Fabiana Morroni Impact of 17-alpha ethinyl estradiol (EE2) and diethyl phthalate (DEP) exposure on microRNAs expression and their target genes in differentiated SH-SY5Y cells Scientific Reports |
| title | Impact of 17-alpha ethinyl estradiol (EE2) and diethyl phthalate (DEP) exposure on microRNAs expression and their target genes in differentiated SH-SY5Y cells |
| title_full | Impact of 17-alpha ethinyl estradiol (EE2) and diethyl phthalate (DEP) exposure on microRNAs expression and their target genes in differentiated SH-SY5Y cells |
| title_fullStr | Impact of 17-alpha ethinyl estradiol (EE2) and diethyl phthalate (DEP) exposure on microRNAs expression and their target genes in differentiated SH-SY5Y cells |
| title_full_unstemmed | Impact of 17-alpha ethinyl estradiol (EE2) and diethyl phthalate (DEP) exposure on microRNAs expression and their target genes in differentiated SH-SY5Y cells |
| title_short | Impact of 17-alpha ethinyl estradiol (EE2) and diethyl phthalate (DEP) exposure on microRNAs expression and their target genes in differentiated SH-SY5Y cells |
| title_sort | impact of 17 alpha ethinyl estradiol ee2 and diethyl phthalate dep exposure on micrornas expression and their target genes in differentiated sh sy5y cells |
| url | https://doi.org/10.1038/s41598-025-86911-1 |
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