Low-dose maternal alcohol consumption: effects in the hearts of offspring in early life and adulthood

Abstract

High alcohol consumption during pregnancy leads to deleterious effects on fetal cardiac structure and it also affects cardiomyocyte growth and maturation. This study aimed to determine whether low levels of maternal alcohol consumption are also detrimental to cardiomyocyte and cardiac growth in the early life of offspring and whether cardiac structure and function in adulthood is affected. Pregnant Sprague–Dawley rat dams were fed a control or 6% (volume/volume) liquid‐based ethanol supplemented (isocaloric) diet throughout gestation. At embryonic day 20, the expression of genes involved in cardiac development was analyzed using Real‐time PCR. At postnatal day 30, cardiomyocyte number, size, and nuclearity in the left ventricle (LV) were determined stereologically. In 8‐month‐old offspring, LV fibrosis and cardiac function (by echocardiography) were examined. Maternal ethanol consumption did not alter gene expression of the cardiac growth factors in the fetus or cardiomyocyte number in weanling offspring. However, at 8 months, there were significant increases in LV anterior and posterior wall thickness during diastole in ethanol‐exposed offspring (P = 0.037 and P = 0.024, respectively), indicative of left ventricular hypertrophy; this was accompanied by a significant increase in fibrosis. Additionally, maximal aortic flow velocity was significantly decreased in ethanol‐exposed offspring (P = 0.035). In conclusion, although there were no detectable early‐life differences in cardiac and cardiomyocyte growth in animals exposed to a chronic low dose of ethanol during gestation, there were clearly deleterious outcomes by adulthood. This suggests that even relatively low doses of alcohol consumed during pregnancy can be detrimental to long‐term cardiac health in the offspring.

Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction

“…In sheep studies of maternal obesity, an accumulation of collagen was also reported [110]. Nguyen et al[111] found cardiac fibrosis in the adult offspring exposed to chronic alcohol consumption during gestation. The presence of cardiac fibrosis is an important determinant of abnormal myocardial stiffness that contributes to diastolic dysfunction [112].…”

Review shows that early foetal alcohol exposure may cause adverse effects even when the mother consumes low levels

“…Animal models involving sheep and mice have been subjected to three different models of alcohol exposure: single occasion binge drinking, ad hoc low‐to‐moderate chronic intake throughout pregnancy and periconceptional exposure before implantation. These experiments showed that all three models had an impact on the development of adult diseases, namely cardiovascular diseases such as hypertension and poorer cardiac recovery after ischaemia, metabolic diseases, including high fasting glucose and insulin, insulin resistance and obesity worsened by a second hit mechanism due to a high‐fat diet, and renal malfunction, defined as inability to concentrate urine .…”

Alcohol-Induced Developmental Origins of Adult-Onset Diseases

“…Growth : Sprague-Dawley rats were fed a liquid diet with or without 6% v/v alcohol throughout gestation, and growth patterns were studied in the offspring up to 1 year; slower growth was detected in males from alcohol-fed dams between 7 and 12 months of age, whereas no differences were found in females (Probyn et al, 2012). Cardiac : Using a low level of 6% v/v alcohol during pregnancy, it was discovered that gene expression of a number of cardiac growth factors in the rat fetus (harvested on gestation day 20) and cardiomyocyte number in weanling offspring (postnatal day 30) were not altered by alcohol, whereas at 8 months age, there were significant increases in left ventricle anterior and posterior wall thickness during diastole in alcohol-exposed offspring (Nguyen et al, 2014). Thyroid : Prenatal alcohol effects on adult thyroid function have been studied in a rat model after 5% (w/v) alcohol was fed during pregnancy.…”

“…It is possible that higher doses of alcohol would lead to birth defects as well as adult-onset diseases, whereas lower doses of alcohol may result in subtle alterations that may not show any visible phenotypes at birth, but would nevertheless result in increased vulnerability to adult-onset disease states (Nguyen et al, 2014). Moreover, early gestation alcohol exposure is likely to produce adverse effects on diverse organs systems, whereas late gestation alcohol exposure is likely to result in tissue- and cell type-specific effects (Waterland and Michels, 2007) and the consequent adult disease outcomes are likely to be different.…”