Abstract
Imbalanced maternal nutrition during gestation can cause alterations of the hypothalamic-pituitary-adrenal (HPA) system in offspring. The present study investigated the effects of maternal low- and high-protein diets during gestation in pigs on the maternal-fetal HPA regulation and expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and 11β-HSD2) and c-fos mRNAs in the placenta and fetal brain. Twenty-seven German Landrace sows were fed diets with high (HP, 30%), low (LP, 6.5%) or adequate (AP, 12.1%) protein levels made isoenergetic by varying the carbohydrate levels. On gestational day 94, fetuses were recovered under general anesthesia for the collection of blood, brain and placenta samples. The LP diet in sows increased salivary cortisol levels during gestation compared to the HP and AP sows and caused an increase of placental GR and c-fos mRNA expression. However, the diurnal rhythm of plasma cortisol was disturbed in both LP and HP sows. Total plasma cortisol concentrations in the umbilical cord vessels were elevated in fetuses from HP sows, whereas corticosteroid-binding globulin levels were decreased in LP fetuses. In the hypothalamus, LP fetuses displayed an enhanced mRNA expression of 11β-HSD1 and a reduced expression of c-fos. Additionally, the 11β-HSD2 mRNA expression was decreased in both LP and HP fetuses. The present results suggest that both low and high protein∶carbohydrate dietary ratios during gestation may alter the expression of genes encoding key determinants of glucocorticoid hormone action in the fetus with potential long-lasting consequences for stress adaptation and health.
Highlights
Experimental and epidemiological studies have led to the hypothesis that exposure to adverse maternal environments during critical periods of fetal growth and development increases the risk of disease in the adult offspring [1]
Pairwise comparison of the diet groups revealed higher salivary cortisol levels in LP sows compared to AP (P,0.05) and HP (P,0.05) sows during gestation
Our results showed a significant effect of gestation stage on maternal salivary cortisol with increasing concentrations in all three diet groups
Summary
Experimental and epidemiological studies have led to the hypothesis that exposure to adverse maternal environments during critical periods of fetal growth and development increases the risk of disease in the adult offspring [1]. Up-regulation of the maternal HPA axis can result in elevated glucocorticoid concentrations in the offspring, contributing to the risk of hypertension, glucose intolerance and obesity [3]. This result is supported by the discovery of an association between reduced birth weight and increased plasma cortisol concentrations in adult human populations [4,5]. Several studies have shown that undernutrition and/or protein deficiency during gestation may produce increased maternal glucocorticoid concentrations, which may restrict fetal growth and cause alterations in endocrine and metabolic systems [6,7,8]. The precise mechanisms linking maternal malnutrition to reduced birth weight and metabolic disease in the offspring are still unknown
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