Prenatal Bisphenol A Exposure Impairs Fetal Heart Development: Molecular and Structural Alterations with Sex-Specific Differences
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals and Treatments
2.2. Western Blot Analysis
2.3. Gelatin Zymography for Matrix Metalloproteinase Activity Detection
2.4. Gene Expression Analysis by qPCR
2.5. Evaluation of Malondialdehyde (MDA) Levels
2.6. Detection of Protein Carbonylation
2.7. Histological Analysis
2.8. Immunofluorescence and Immunohistochemistry
2.9. Statistical Analysis
3. Results
3.1. Prenatal BPA Exposure Alters Estrogen Receptor Expression in a Sex-Specific Manner in the Fetal Rat Heart
3.2. Prenatal BPA Exposure Triggers Inflammation, Oxidative Stress, and Ferroptosis in the Fetal Rat Heart
3.3. Prenatal BPA Exposure Affects Markers of Cardiac Distension, Remodeling, and Fibrosis in the Fetal Rat Heart
3.4. Prenatal BPA Exposure Induces Histological Alterations in the Fetal Rat Heart
4. Discussion
Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ACSL4 | acyl-CoA synthetase long-chain family member 4 |
ANP | Atrial Natriuretic Peptide |
BNP | Brain Natriuretic Peptide |
BPA | Bisphenol A |
BPA-GA | BPA-glucuronide |
CAT | Catalase |
Col1A1 | Collagen type I alpha 1 chain |
Col3A1 | Collagen type III alpha 1 chain |
CTGF | Connective tissue growth factor |
CVD | Cardiovascular disease |
ECM | Extracellular matrix |
EDCs | Endocrine-disrupting chemicals |
ER | Estrogen receptor |
EtOH | Ethanol |
GPR30/GPER | G protein-coupled estrogen receptor 30 |
GPX4 | Glutathione peroxidase 4 |
H.E. | Hematoxylin and eosin |
hiPSC | Human-induced pluripotent stem cell |
IL-1β | Interleukin-1β |
MMPs | Matrix metalloproteinases |
NF-κB | Nuclear Factor kappa B |
NLRP3 | NOD-like receptor protein 3 |
qPCR | Quantitative real-time PCR |
SELENOT | Selenoprotein T |
SERM | Selective estrogen receptor modulator |
SOD | Superoxide dismutase |
TGF-β | Transforming growth factor-β |
TNF-α | Tumor necrosis factor-α |
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Gene Accession Number | Forward Primer 5′-3′ | Reverse Primer 5′-3′ |
---|---|---|
NM_031512 (Il-1β) | -CCCAGGACATGCTAGGGAGCC- | -AGGCAGGGAGGGAAACACACG- |
NM_012675.3 (Tnf-α) | -CACCACGCTCTTCTGTCTACTG- | -GCTACGGGCTTGTCACTCG- |
NM_012612.2 (NppA) | -GGAAGTCAACCCGTCTCAGA- | -TGGGCTCCAATCCTGTCAAT- |
NM_031545.1 (NppB) | -CCAGAACAATCCACGATGCA- | -GCAGCTTGAACTATGTGCCA- |
NM_053304.1 (Col1A1) | -GACATGTTCAGCTTTGTGGACCT- | -AGGGACCCTTAGGCCATTGTGTA- |
NM_032085.1 (Col3A1) | -TTTGGCACAGCAGTCCAATGTA- | -GACAGATCCCGAGTCGCAGA- |
NM_021578.2 (Tgf-β) | -AACCGACCCTTCCTGCTCCT- | -TCCACTTCCAACCCAGGTCCT- |
NR_046237.2 (18s rRNA) | -CATTCGAACGTCTGCCCTAT- | -GTTTCTCAGGCTCCCTCTCC- |
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Marrone, A.; De Bartolo, A.; Rago, V.; Conforti, F.; Urlandini, L.; Angelone, T.; Mazza, R.; Mandalà, M.; Rocca, C. Prenatal Bisphenol A Exposure Impairs Fetal Heart Development: Molecular and Structural Alterations with Sex-Specific Differences. Antioxidants 2025, 14, 863. https://doi.org/10.3390/antiox14070863
Marrone A, De Bartolo A, Rago V, Conforti F, Urlandini L, Angelone T, Mazza R, Mandalà M, Rocca C. Prenatal Bisphenol A Exposure Impairs Fetal Heart Development: Molecular and Structural Alterations with Sex-Specific Differences. Antioxidants. 2025; 14(7):863. https://doi.org/10.3390/antiox14070863
Chicago/Turabian StyleMarrone, Alessandro, Anna De Bartolo, Vittoria Rago, Francesco Conforti, Lidia Urlandini, Tommaso Angelone, Rosa Mazza, Maurizio Mandalà, and Carmine Rocca. 2025. "Prenatal Bisphenol A Exposure Impairs Fetal Heart Development: Molecular and Structural Alterations with Sex-Specific Differences" Antioxidants 14, no. 7: 863. https://doi.org/10.3390/antiox14070863
APA StyleMarrone, A., De Bartolo, A., Rago, V., Conforti, F., Urlandini, L., Angelone, T., Mazza, R., Mandalà, M., & Rocca, C. (2025). Prenatal Bisphenol A Exposure Impairs Fetal Heart Development: Molecular and Structural Alterations with Sex-Specific Differences. Antioxidants, 14(7), 863. https://doi.org/10.3390/antiox14070863