Abstract
Nonalcoholic fatty liver disease patients are characterized by hepatic steatosis. Prenatal glucocorticoid overexposure can result in steatosis. In this study, we aimed to determine the mechanism and cellular apoptosis of prenatal glucocorticoid overexposure in rats and whether melatonin can rescue the prenatal glucocorticoid-induced steatosis and apoptosis in neonatal rats. Pregnant Sprague-Dawley rats at gestational days 14 to 21 were administered dexamethasone. Acute effects of prenatal programming liver were assessed at postnatal day 7. The expression of proteins involved in the apoptotic and methylation pathways was analyzed by RT-PCR and Western blotting. Apoptosis and steatosis were examined by histology staining. The liver steatosis and apoptosis were increased in prenatal glucocorticoid group more than in control group and decreased in melatonin group. The expression of leptin decreased in prenatal glucocorticoid and increased in melatonin group by liver RT-PCR and Western blot study. Caspase 3, TNF-α proteins expression, and TUNEL stains increased in prenatal glucocorticoid compared with control and decreased in melatonin group. The liver histone deacetylase, DNA methyltransferase activity, and DNA methylation were increased in prenatal glucocorticoid and decreased in melatonin group. The present study showed that the prenatal glucocorticoid induced programming liver steatosis at day 7 after delivery, possibly via altered leptin expression. Melatonin can reverse the methylation of leptin and decreased liver steatosis.
Highlights
7% of pregnant women are at risk of preterm delivery and these women are routinely treated with synthetic glucocorticoids to improve neonatal outcome [1]
The liver steatosis was studied by oil red and it was overexpressed in the prenatal steroid group more than in the control group and downexpressed in the melatonin group (Figures 1(a)–1(d))
Realtime PCR showed that leptin decreased in prenatal steroid group more than in control group and recovered in melatonin group in liver (Figure 2(a))
Summary
7% of pregnant women are at risk of preterm delivery and these women are routinely treated with synthetic glucocorticoids to improve neonatal outcome [1]. Factors such as prenatal exposure to glucocorticoids can all have negative health consequences for the offspring that persist into adulthood [2, 3]. Prenatal glucocorticoids overexposure in rats increases susceptibility to fatty liver disease. This may be due to depot-specific-programmed alterations in fat metabolism [4, 5]. It is important to plan a strategy to rescue the liver steatosis
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