Liquid-Diet with Alcohol Alters Maternal, Fetal and Placental Weights and the Expression of Molecules Involved in Integrin Signaling in the Fetal Cerebral Cortex

Ujjwal K Rout,Julie M Dhossche

doi:10.3390/ijerph7114023

Abstract

Maternal alcohol consumption during pregnancy causes wide range of behavioral and structural deficits in children, commonly known as Fetal Alcohol Syndrome (FAS). Children with FAS may suffer behavioral deficits in the absence of obvious malformations. In rodents, the exposure to alcohol during gestation changes brain structures and weights of offspring. The mechanism of FAS is not completely understood. In the present study, an established rat (Long-Evans) model of FAS was used. The litter size and the weights of mothers, fetuses and placentas were examined on gestation days 18 or 20. On gestation day 18, the effects of chronic alcohol on the expression levels of integrin receptor subunits, phospholipase-Cγ and N-cadherin were examined in the fetal cerebral cortices. Presence of alcohol in the liquid-diet reduced the consumption and decreased weights of mothers and fetuses but increased the placental weights. Expression levels of β1 and α3 integrin subunits and phospholipase-Cγ2 were significantly altered in the fetal cerebral cortices of mothers on alcohol containing diet. Results show that alcohol consumption during pregnancy even with protein, mineral and vitamin enriched diet may affect maternal and fetal health, and alter integrin receptor signaling pathways in the fetal cerebral cortex disturbing the development of fetal brains.

Highlights

Alcohol consumption during pregnancy disturbs the normal development of fetus causing wide range of structural and behavioral problems in children commonly known as fetal alcohol syndrome (FAS) [1]
Results presented here show for the first time that (i) the pregnant Long-Evans rats consumed significantly less of a protein fortified liquid-diet (F1265SP) when the alcohol in the diet is increased in a step-wise manner and (ii) that in this species of rat, the expression of molecules involved in the integrin signaling are significantly altered in the cerebral cortices of fetuses exposed to alcohol during gestation even in the absence of obvious morphological defects in the offspring
The prenatal alcohol decreases the expression levels of phospholipase C (PLC)-γ2 isoform in the cerebral cortices, an isoform that is known to influence integrin signaling in osteoclast [44]. These results indicate that prenatal alcohol may alter integrin mediated signaling and functions in the developing cerebral cortices by altering the expression of β1 and α3 integrin subunits, and PLC-γ2

Summary

Introduction

Alcohol consumption during pregnancy disturbs the normal development of fetus causing wide range of structural and behavioral problems in children commonly known as fetal alcohol syndrome (FAS) [1]. Reduced birth weight and mental deficiencies are the hallmarks of FAS that persists even in adolescence [2]. Several studies with Long-Evans rats show that the migration and proliferation of fetal cerebral cortical neurons is altered by prenatal alcohol even when the alcohol in the protein- and nutrient-enriched liquid-diet is increased in a gradual and step-wise manner [10,11,12,13]. In vitro studies with slice culture of fetal cerebral cortex from Sprague-Dawley rats reveal that alcohol may alter the expression of integrin subunits that are involved in the migration of neurons [14]. The effects of prenatal alcohol on maternal diet consumption, and the weights of mother, fetus and placenta in

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