Alcohol-induced placental vasculopathy reprograms the placental-fetal cardiovascular axis: angiogenic mechanisms linking maternal alcohol exposure to developmental cardiovascular programming
- 1Laboratorio de Reproducción y Fisiología Materno-Embrionaria, Departamento de Biodiversidad y Biología Experimental (DBBE), Instituto de Biodiversidad y Biología Experimental y Aplicada (IBBEA), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Abstract
Among prenatal insults, maternal alcohol consumption has emerged as an important determinant of fetal cardiovascular development and long-term cardiovascular disease susceptibility. Growing evidence indicates that the placenta is a central biological mediator linking maternal alcohol exposure with abnormal fetal cardiac development. This review integrates current experimental and clinical findings on the developmental relationship between placental vascularization and fetal cardiogenesis, highlighting the placental-embryofetal cardiovascular axis as a conceptual framework for alcohol-induced cardiopathy programming. We examine evidence that prenatal alcohol exposure disrupts placental vascular development through impaired decidual spiral artery angiogenesis and remodeling and altered trophoblast differentiation and invasion, and labyrinthine vascularization. Experimental studies suggest that oxidative stress and hypoxia perturb interconnected angiogenic vascular endothelial growth factor (VEGF)-nitric oxide synthases (NOS)-matrix metalloproteinases (MMPs) pathways, and related redox-sensitive mediators, ultimately compromising placental perfusion and fetoplacental hemodynamics. We further discuss that placental dysfunction may alter the molecular, metabolic, endocrine, oxygen-dependent, and hemodynamic signals regulating fetal cardiac development, potentially affecting myocardial morphogenesis, cardiac remodeling, coronary vascularization, septation, valvulogenesis, and cardiovascular maturation during critical developmental windows. Collectively, available evidence supports a model in which disruption of placental angiogenic homeostasis may represent a key intermediary linking maternal alcohol exposure with fetal cardiovascular programming. This perspective integrates direct embryofetal effects with indirect placental-mediated mechanisms and highlights the need to clarify their relative contributions across developmental windows. Improved understanding of the placental-embryofetal cardiovascular axis may facilitate identification of early biomarkers and preventive or therapeutic strategies to reduce the lifelong cardiovascular consequences of prenatal alcohol exposure.
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BibTeX
@article{cebral2026alcoholinduced,
title = {{Alcohol-induced placental vasculopathy reprograms the placental-fetal cardiovascular axis: angiogenic mechanisms linking maternal alcohol exposure to developmental cardiovascular programming}},
author = {Elisa Cebral},
journal = {Frontiers in Physiology},
year = {2026},
month = oct,
doi = {10.3389/fphys.2026.1917947},
url = {https://doi.org/10.3389/fphys.2026.1917947},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Alcohol-induced placental vasculopathy reprograms the placental-fetal cardiovascular axis: angiogenic mechanisms linking maternal alcohol exposure to developmental cardiovascular programming
AU - Elisa Cebral
PY - 2026
DA - 2026/10/12
JO - Frontiers in Physiology
DO - 10.3389/fphys.2026.1917947
UR - https://doi.org/10.3389/fphys.2026.1917947
AB - Among prenatal insults, maternal alcohol consumption has emerged as an important determinant of fetal cardiovascular development and long-term cardiovascular disease susceptibility. Growing evidence indicates that the placenta is a central biological mediator linking maternal alcohol exposure with abnormal fetal cardiac development. This review integrates current experimental and clinical findings on the developmental relationship between placental vascularization and fetal cardiogenesis, highlighting the placental-embryofetal cardiovascular axis as a conceptual framework for alcohol-induced cardiopathy programming. We examine evidence that prenatal alcohol exposure disrupts placental vascular development through impaired decidual spiral artery angiogenesis and remodeling and altered trophoblast differentiation and invasion, and labyrinthine vascularization. Experimental studies suggest that oxidative stress and hypoxia perturb interconnected angiogenic vascular endothelial growth factor (VEGF)-nitric oxide synthases (NOS)-matrix metalloproteinases (MMPs) pathways, and related redox-sensitive mediators, ultimately compromising placental perfusion and fetoplacental hemodynamics. We further discuss that placental dysfunction may alter the molecular, metabolic, endocrine, oxygen-dependent, and hemodynamic signals regulating fetal cardiac development, potentially affecting myocardial morphogenesis, cardiac remodeling, coronary vascularization, septation, valvulogenesis, and cardiovascular maturation during critical developmental windows. Collectively, available evidence supports a model in which disruption of placental angiogenic homeostasis may represent a key intermediary linking maternal alcohol exposure with fetal cardiovascular programming. This perspective integrates direct embryofetal effects with indirect placental-mediated mechanisms and highlights the need to clarify their relative contributions across developmental windows. Improved understanding of the placental-embryofetal cardiovascular axis may facilitate identification of early biomarkers and preventive or therapeutic strategies to reduce the lifelong cardiovascular consequences of prenatal alcohol exposure.
SN - 1664-042X
ER -