Oxidative stress and cellular and tissue damage in organogenic outbred mouse embryos after moderate perigestational alcohol intake

Abstract

Perigestational alcohol consumption by CF-1 mouse, from before mating up to the period of embryo organogenesis, leads to retarded early embryo development and neural tube defects. Here, we addressed if perigestational alcohol ingestion up to Day 10 of pregnancy induces oxidative stress and changes in macromolecules and organ tissues of early organogenic embryos. Adult CF-1 female mice were administered 10% ethanol in their drinking water for 17 days prior to mating and until Day 10 of gestation, whereas control females were administered ethanol-free water. Our results demonstrated significantly reduced Catalase abundance and activity and increased glutathione content in the embryos of ethanol-treated females. The nitrite level was significantly reduced, but TBARS (thiobarbituric acid reactive substances) content, an index of lipid peroxidation, did not change. Embryos derived from ethanol-treated females also showed higher abundance of 3-nitrotyrosine (3-NT)-containing proteins in all tissues, compared to the control group. Apoptosis was significantly increased in the ectoderm and mesoderm, but not in the heart-although this organ did contain more cleaved Caspase-3-positive cardiomyocytes per area of ventricular myocardium than controls. In sum, moderate perigestational alcohol ingestion up to Day 10 of gestation in mice induces oxidative stress by altering radical nitrogen species and antioxidant enzymatic and non-enzymatic mechanisms in embryos. Further, generalized protein nitration, due to unbalanced nitric oxide levels associated with tissue-specific apoptosis, was detected in embryos, suggesting that oxidative mechanisms may play an important role in the perigestational alcohol-induced malformation of organogenic embryos exposed to ethanol.

Ethanol exposure in prenatal and early postnatal induced cardiac injury in rats: involvement of oxidative stress, Hsp70, ERK 1/2, JNK, and apoptosis in a 3-month follow-up study

“…In spite of the past few decades of research, our understanding of the pathogenesis of alcohol cardiotoxicity in pups is still limited. Important progress in this field has been the appreciation of the role of oxidative stress and apoptosis in the pathogenesis of alcohol heart damage (Coll et al 2017;Shirpoor et al 2015).…”

Abnormal growth and morphogenesis of placenta at term is linked to adverse fetal development after perigestational alcohol consumption up to early gestation in mouse

“…Usually, chronic drinker women consume two glasses of 11% wine per day (18–30 g absolute ethanol/day, or 14 or more drinks per week (Colvin et al, 2007; Muggli et al, 2016; Wallace et al, 2007), levels of ethanol consumption associated with a risk of FAS or low birth weight. In our model of perigestational alcohol intake, the ingestion of about 17–20 g ethanol/kg/day can generate low blood alcohol concentration of 24.5 mg/dl (about 5 mM) (Coll et al, 2017), mimicking women who consumed one to three drinks per day. More than 14 g absolute ethanol/day can lead to a risk of FAS or high frequency of babies with low birth weight.…”

“…Thus, we have shown, in mouse, that moderate oral ethanol intake for 2 weeks before pregnancy and up to peri‐implantational stages affect the embryo differentiation and growth and leads to retardation during implantation (Pérez‐Tito, Bevilacqua, & Cebral, 2014). Also perigestational alcohol ingestion up to early mouse organogenesis (day 10 of gestation) induces delayed embryo development, reduces viability, produces dysmorphogenesis of neural tube, deregulates the embryonic cadherin expression (Coll et al, 2011), alters the arachidonic acid metabolic pathways (Cebral et al, 2007), and generates embryo oxidative stress (Coll et al, 2017), among other effects.…”

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

“…Paralely, the PACinduced deficient labyrinthine vasculogenesis is associated to a densely packed tissue due to increased chorionic trophoblastic cell proliferation (Gualdoni G. S. et al, 2021; Figure 2G). The early insufficient labyrinthine vascularization generates persistent hypoxia and OS and embryo growth restriction and malformations at organogenesis (Cebral et al, 2007;Coll et al, 2011Coll et al, , 2017Gualdoni G. S. et al, 2021).…”

“…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. Perigestational alcohol intake up to organogenesis (equivalent to the first three-four weeks of human pregnancy) induces delayed embryo differentiation and growth, and dysmorphogenesis, by altering molecular pathways, genotoxicity, apoptosis and oxidative stress (OS) (Cebral et al, 2007(Cebral et al, , 2011Coll et al, 2011Coll et al, , 2017. However, 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).…”