Early Abnormal Placentation and Evidence of Vascular Endothelial Growth Factor System Dysregulation at the Feto-Maternal Interface After Periconceptional Alcohol Consumption

GUALDONI, GISELA SOLEDAD; JACOBO P; BARRIL C; VENTUREIRA M.; CEBRAL E

Vascular Dysfunction Beyond Pathological Pregnancies. An International Effort Addressed to Fill the Gaps in Latin America

Frontiers Editorial Office

Año: 2024; p. 174 - 186

Adequate placentation, placental tissue remodeling and vascularization is essentialfor the success of gestation and optimal fetal growth. Recently, it was suggestedthat abnormal placenta induced by maternal alcohol consumption may participatein fetal growth restriction and relevant clinical manifestations of the Fetal AlcoholSpectrum Disorders (FASD). Particularly, periconceptional alcohol consumption up toearly gestation can alter placentation and angiogenesis that persists in pregnancybeyond the exposure period. Experimental evidence suggests that abnormal placentafollowing maternal alcohol intake is associated with insufficient vascularization anddefective trophoblast development, growth and function in early gestation. Accumulateddata indicate that impaired vascular endothelial growth factor (VEGF) system, includingtheir downstream effectors, the nitric oxide (NO) and metalloproteinases (MMPs), isa pivotal spatio-temporal altered mechanism underlying the early placental vascularalterations induced by maternal alcohol consumption. In this review we propose thatthe periconceptional alcohol intake up to early organogenesis (first trimester) altersthe VEGF-NO-MMPs system in trophoblastic-decidual tissues, generating imbalancesin the trophoblastic proliferation/apoptosis, insufficient trophoblastic development,differentiation and migration, deficient labyrinthine vascularization, and uncompletedremodelation and transformation of decidual spiral arterioles. Consequently, abnormalplacenta with insufficiency blood perfusion, vasoconstriction and reduced labyrinthineblood exchange can be generated. Herein, we review emerging knowledge of abnormalplacenta linked to pregnancy complications and FASD produced by gestationalalcohol ingestion and provide evidence of the early abnormal placental angiogenesisvascularization and growth associated to decidual-trophoblastic dysregulation ofVEGF system after periconceptional alcohol consumption up to mid-gestation, in amouse model.