An inadequate maternal dietary protein level during pregnancy in pigs alters the expression of corticosteroid receptors and 11β-hydroxysteroid dehydrogenase isoforms in the placenta and fetal brain
Ellen Kanitz, Maria Gräbner, Margret Tuchscherer, Klaus-Peter Brüssow, Bernd Stabenow, Charlotte Rehfeldt, Cornelia C Metges & Winfried Otten
Imbalanced maternal nutrition during pregnancy can cause fetal growth retardation, metabolic changes and alterations of the hypothalamicpituitaryadrenal (HPA) system in the offspring. Here, we investigated the effects of maternal low and high protein diets during pregnancy in pigs on materno-fetal HPA regulation and expression of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and 11β-HSD2) mRNA in the placenta and fetal brain. Twenty-four German Landrace sows were fed isoenergetic diets with high (HP, 30%), low (LP, 6%) or control (CP, 12%) protein levels throughout pregnancy. On gestational day 93, fetuses were recovered under general anaesthesia for the collection of blood and brain samples. In pregnant sows, the LP diet reduced growth performance and increased salivary cortisol levels. Number and body weight of fetuses were not affected by the maternal diets. Total plasma cortisol concentrations in the umbilical vein and artery as well as in endogenous blood circulation were significantly elevated in fetuses from HP sows, whereas corticosteroid-binding globulin levels were significantly decreased in LP fetuses compared to controls. Indeed, the calculated free cortisol index displayed increased concentrations of biologically active cortisol in fetuses from LP sows. In the placenta, the LP diet caused a significant increase of GR mRNA expression, but affected neither the 11β-HSD1 and 11β-HSD2 mRNA expression nor the enzyme activity. However, there was an effect of the LP diet on the 11β-HSD mRNA expression in the fetal brain. The hypothalamic 11β-HSD1 mRNA expression was significantly enhanced in LP fetuses compared to controls, whereas the 11β-HSD2 mRNA expression was decreased. There was no dietary effect on the expression of glucocorticoid regulating genes in the fetal hippocampus. In conclusion, we demonstrated that an inadequate maternal dietary protein level during pregnancy in pigs tissue-specifically affects the materno-fetal HPA regulation. Furthermore, the present results suggest that a dietary protein deficiency during pregnancy may alter the expression of genes encoding key determinants of glucocorticoid hormone action in the fetus.