مرکز منطقه ای اطلاع رساني علوم و فناوري - Alcohol exposure in utero perturbs retinoid homeostasis in adult rats

Author/Authors :

kim, youn-kyung rutgers university - rutgers center for lipid research - department of food science,, New Brunswick, USA , zuccaro, michael v. rutgers university - rutgers center for lipid research - department of food science, New Brunswick, USA , zhang, changqing rutgers university - department of animal sciences and endocrine research program, New Brunswick, USA , sarkar, dipak rutgers university - department of animal sciences and endocrine research program, New Brunswick, USA , quadro, loredana rutgers university - rutgers center for lipid research - department of food science, New Brunswick, usa

Abstract :

Background: Maternal alcohol exposure and adult alcohol intake have been shown to perturb themetabolism of various micro- and macro-nutrients, including vitamin A and its derivatives (retinoids).Therefore, it has been hypothesized that the well-known detrimental consequences of alcohol consumptionmay be due to deregulations of the metabolism of such nutrients rather than to a direct effect of alcohol.Alcohol exposure in utero also has long-term harmful consequences on the health of the offspring withmechanisms that have not been fully clarified. Disruption of tissue retinoid homeostasis has been linkednot only to abnormal embryonic development, but also to various adult pathological conditions, includingcancer, metabolic disorders and abnormal lung function. We hypothesized that prenatal alcohol exposuremay permanently perturb tissue retinoid metabolism, predisposing the offspring to adult chronic diseases.Methods: Serum and tissues (liver, lung and prostate from males; liver and lung from females) werecollected from 60-75 day-old sprague dawley rats born from dams that were: (I) fed a liquid diet containing6.7% alcohol between gestational day 7 and 21; or (II) pair-fed with isocaloric liquid diet during the samegestational window; or (III) fed ad libitum with regular rat chow diet throughout pregnancy. Serum andtissue retinoid levels were analyzed by reverse-phase high-performance liquid chromatography (HPLC).Serum retinol-binding protein (RBP) levels were measured by western blot analysis, and liver, lung andprostate mRNA levels of lecithin-retinol acyltransferase (LRAT) were measured by qPCR.Results: Retinyl ester levels were significantly reduced in the lung of both males and females, as well asin the liver and ventral prostate of males born from alcohol-fed dams. Tissue LRAT mRNA levels remainedunchanged upon maternal alcohol treatment.Conclusions: Prenatal alcohol exposure in rats affects retinoid metabolism in adult life, in a tissue- andsex-dependent manner. We propose that the alcohol-induced perturbations of vitamin A metabolism maypredispose to detrimental consequnces on adult health.