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

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.

Dietary adenosine supplementation improves placental angiogenesis in IUGR piglets by up-regulating adenosine A2a receptor

“…The placenta plays an important role in fetal growth ( Reynolds et al., 2006 ; Zhao et al., 2020 ), and adequate placental angiogenesis is essential for successful pregnancy and optimal growth of the fetus ( Gualdoni et al., 2021 ). Thus, to further explore the different effects of adenosine on Normal and IUGR fetuses, the placentae from IUGR and normal-weight (Normal) fetuses were separately collected as 2 groups for further analysis.…”

The role of maternal choline, folate and one‐carbon metabolism in mediating the impact of prenatal alcohol exposure on placental and fetal development

“…DNA methyltransferases (DNMTs) catalyse the transfer of methyl groups from SAM to DNA establishing optimal DNAm for the transcription of growth factors such as vascular endothelial growth factor (Vegfa) and other proteins involved in trophoblast invasion such as matrix metalloproteinases (Rahat et al., 2022 ). PAE reduces expression of RFC (Keating et al., 2009 ) and activity of MTR (Barak et al., 2002 ), which may alter DNAm and transcription of growth factors, thereby impacting on trophoblast invasion and placentation (Gualdoni et al., 2021 ; Williams et al., 2011 ). Supplementation with choline probably provides alternate methyl donors in the maternal liver, sparing folate and producing additional SAM and methionine for delivery to the placenta (Steane et al., 2022 ), normalising DNAm, gene transcription and placentation.…”

A decidualizáció klinikai vonatkozásai

“…Számos kísérleti adat igazol ja például, hogy a perikoncepcionális alkoholfogyasztás (első trimeszter) megzavarja a trophoblast proliferáció/ apoptózis egyensúlyát, a differenciálódást és migrációt, vagyis a korai ereződési folyamatokat, beleértve a spirális artériák átalakulását is. Ennek következtében a tropho blastok angiogén hatásai sérülnek: megváltozik a VEGF-NO-MMP rendszer működése, ami a placenta vascula risatiós zavaraihoz és ennek megfelelően a magzati oxigénellátás zavarához vezet [36]. Az oxigénellátás za varai (hypoxia, hyperoxia, fokozott ROStermelődés) a bolyhok syncytiotrophoblastrétegében kondenzáltkro matintartalmú fürtökbe rendeződött sejtmagoknak, úgynevezett syncytialis csomóknak a megjelenéséhez ve zetnek, melyek biomarkerként használhatók szövődmé nyes terhességekben.…”