Abstract
Adequate placentation, placental tissue remodeling and vascularization is essential for the success of gestation and optimal fetal growth. Recently, it was suggested that abnormal placenta induced by maternal alcohol consumption may participate in fetal growth restriction and relevant clinical manifestations of the Fetal Alcohol Spectrum Disorders (FASD). Particularly, periconceptional alcohol consumption up to early gestation can alter placentation and angiogenesis that persists in pregnancy beyond the exposure period. Experimental evidence suggests that abnormal placenta following maternal alcohol intake is associated with insufficient vascularization and defective trophoblast development, growth and function in early gestation. Accumulated data indicate that impaired vascular endothelial growth factor (VEGF) system, including their downstream effectors, the nitric oxide (NO) and metalloproteinases (MMPs), is a pivotal spatio-temporal altered mechanism underlying the early placental vascular alterations induced by maternal alcohol consumption. In this review we propose that the periconceptional alcohol intake up to early organogenesis (first trimester) alters the VEGF-NO-MMPs system in trophoblastic-decidual tissues, generating imbalances in the trophoblastic proliferation/apoptosis, insufficient trophoblastic development, differentiation and migration, deficient labyrinthine vascularization, and uncompleted remodelation and transformation of decidual spiral arterioles. Consequently, abnormal placenta with insufficiency blood perfusion, vasoconstriction and reduced labyrinthine blood exchange can be generated. Herein, we review emerging knowledge of abnormal placenta linked to pregnancy complications and FASD produced by gestational alcohol ingestion and provide evidence of the early abnormal placental angiogenesis-vascularization and growth associated to decidual-trophoblastic dysregulation of VEGF system after periconceptional alcohol consumption up to mid-gestation, in a mouse model.
Highlights
Normal growth and survival of the fetus depends on the adequate placentation
Maternal alcohol consumption can lead to the irreversible condition of fetal alcohol syndrome (FAS), the most severe form of the alcohol spectrum disorders (FASDs) (Guerri et al, 2009; de Sanctis et al, 2011; May and Gossage, 2011; Memo et al, 2013; Joya et al, 2015; Van Heertum and Rossi, 2017)
Despite the direct effects of ethanol exposure on embryo-fetal outcomes, placental injury due to maternal alcohol ingestion was recently proposed as an indirect cause of fetal abnormalities and FASD (Gupta et al, 2016)
Summary
Normal growth and survival of the fetus depends on the adequate placentation. Besides providing sufficient amounts of nutrients and oxygen, the placenta establishes a privileged immune environment for fetal growth by orchestrating maternal adaptations to pregnancy and acting as a selective and protective barrier to prevent feto-maternal diseases (Creeth and John, 2020). Despite public efforts to reduce prevalence of alcohol consumption, still high proportion of women often continues to drink moderate levels of alcohol (200 ml/day of wine containing ethanol 11%) during the early pregnancy while unaware they are pregnant (4 to 6 weeks after conception during early organogenesis) (Colvin et al, 2007) In this relation, recently we established a mouse model of perigestational moderate alcohol ingestion, previous and up to early gestation, to study the embryo developmental effects compatible with FASD. The etiology of abnormal placenta associated to maternal alcohol consumption is proposed to be related to gestational windows of susceptibility: peri-implantation, gastrulation and/or organogenesis (first trimester in human) (Livy et al, 2004) Both early alcohol and acetaldehyde exposure may contribute to the pathogenesis of FASD by reducing placental growth and function on the first trimester (Lui et al, 2014). We first provide a brief background on the gestational alcohol placental defects as the etiology of FASD, and we extend the revision to the knowledge of emerging evidences on the effects of periconceptional consumption up to early organogenesis on placental development, highlighting the role of the trophoblastdecidual VEGF system in a mouse model
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