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Maternal Ethanol Exposure-Induced Cardiac Fibrosis is Associated with Changes in TGF-β and SIRT1/FOXO3a Signaling in Male Rat Offspring: A Three-Month Follow-up Study


Ethanol exposure during pregnancy induces cardiac fibrosis in the fetal heart. However, the mechanisms by which consumption of ethanol induces fibrotic changes are not known. Pregnant rats were received ethanol 4.5 g/kg BW once per day from the 7th day of pregnancy (GD7) throughout lactation. Our findings demonstrated that, area of fibrosis increased in cardiac tissue in the pups on both postnatal day twenty one (PN21) and postnatal day ninety (PN90) after prenatal and early postnatal period ethanol treatment compared with the controls. It was accompanied by a decline in the expression of SIRT1 protein along with the elevation of FOXO3a and TGF-β protein expressions which were determined by western blot. Overall, our data reveal that prenatal alcohol usage increase in fibrotic regions in the pup hearts possibly by regulating TGF-β, FOXO3a and SIRT1 protein levels. These are potential therapeutic molecular targets that can be modulated to protect heart against maternal ethanol exposure.

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Data Availability

The datasets generated during and/or analyzed during this study are available from the corresponding author on reasonable request.


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This study was supported by school of medicine, Urmia University of Medical Sciences, Urmia, Iran.

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AS: Data curation., Methodology., Writing—review & editing. RN: Conceptualization., Formal analysis., Methodology., Project administration., Supervision., Validation., Visualization., Writing—original draft., Writing—review & editing.

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Correspondence to Roya Naderi.

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Shirpoor, A., Naderi, R. Maternal Ethanol Exposure-Induced Cardiac Fibrosis is Associated with Changes in TGF-β and SIRT1/FOXO3a Signaling in Male Rat Offspring: A Three-Month Follow-up Study. Cardiovasc Toxicol 22, 858–865 (2022).

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  • Ethanol
  • Offspring
  • SIRT1
  • FOXO3a
  • TGF-β
  • Heart