Cellular and molecular oxidative stress-related effects in uterine myometrial and trophoblast-decidual tissues after perigestational alcohol intake up to early mouse organogenesis

Abstract

The placenta plays a major role in embryo-fetal defects and intrauterine growth retardation after maternal alcohol consumption. Our aims were to determine the oxidative status and cellular and molecular oxidative stress effects on uterine myometrium and trophoblast-decidual tissue following perigestational alcohol intake at early organogenesis. CF-1 female mice were administered with 10% alcohol in drinking water for 17 days prior to and up to day 10 of gestation. Control females received ethanol-free water. Treated mice had smaller implantation sites compared to controls (p < 0.05), diminished maternal vascular lumen, and irregular/discontinuous endothelium of decidual vessels. The trophoblast giant cell layer was disorganized and presented increased abnormal nuclear frequency. The myometrium of treated females had reduced nitrite content, increased superoxide dismutase activity, and reduced glutathione (GSH) content (p < 0.05). However, the trophoblast-decidual tissue of treated females had increased nitrite content (p < 0.05), increased GSH level (p < 0.001), increased thiobarbituric acid-reactive substance concentration (p < 0.001), higher 3-nitrotyrosine immunoreaction, and increased apoptotic index (p < 0.05) compared to controls. In summary, perigestational alcohol ingestion at organogenesis induced oxidative stress in the myometrium and trophoblast-decidual tissue, mainly affecting cells and macromolecules of trophoblast and decidual tissues around early organogenesis, in CF-1 mouse, and suggests that oxidative-induced abnormal early placental formation probably leads to risk of prematurity and fetal growth impairment at term.

Ethanol consumption during gestation promotes placental alterations in IGF-1 deficient mice

“…Ethanol consumption during gestation can lead to an altered trophoblast motility and invasion, resulting in a distorted placental barrier thickness and abnormal development that can promote an aberrant nutrient exchange, producing impairments in fetal growth and development. 39,40 The statistical tests used were Mann-Whitney U or Student T test to compare between two groups, and general linear model to evaluate the effect of the two independent variables in the present study (ethanol consumption and IGF-1 deficiency). Differences were considered significant at a level of p < 0.05.…”

Alcohol Consumption During Pregnancy and Risk of Placental Abnormality: The Japan Environment and Children’s Study

“…Trophoblast invasion into the uterus is a key process during human placentation. In mice, perigestational alcohol exposure at organogenesis induced oxidative stress in the myometrium and trophoblast-decidual tissue, mainly affecting cells and macromolecules of trophoblasts and decidual tissues associated with placental formation 24 . Han et al .…”

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

“…Although antioxidant enzymatic and glutathione activities have been shown in the placenta after gestational alcohol ingestion (Qanungo and Mukherjea, 2000), OS impacts strongly on trophoblastic function and leads to pregnancy loss (Gundogan et al, 2010). Perigestational moderate alcohol ingestion up to organogenesis in mouse produces protein nitration, lipid peroxidation and DNA damage in trophoblast-decidual tissue (Coll et al, 2018). As a result of alcohol-induced OS and decreased bioavailability of NO, insufficient early placental vascularization and arteriolar vasoconstriction can cause placental hypoxia (Acevedo et al, 2001;Wareing et al, 2006;Gualdoni G. S. et al, 2021).…”

“…Particularly, perigestational moderate alcohol consumption up to peri-implantation prevents blastocyst implantation and results in early pregnancy loss (Perez-Tito et al, 2014). Since maternal alcohol exposure can decrease the trophoblast migration/invasion leading to abnormal placental vascularization (Han et al, 2012), the link between placental vasculopathy and failure in the early decidualtrophoblast development and dysregulation of angiogenesisvascularization after perigestational alcohol ingestion up to organogenesis recently began to be studied in mouse models (Coll et al, 2018;Ventureira et al, 2019;Gualdoni G. S. et al, 2021).…”