Effect of ~ 25 days cortisol treatment on late gestation placenta

Previous studies have suggested that increases in maternal cortisol or maternal stress in late pregnancy increase the risk of stillbirth at term. In an ovine model with increased maternal cortisol over the last 0.20 of gestation, we have previously found evidence of disruption of fetal serum and cardiac metabolomics, and of expression of genes related to mitochondrial function and metabolism in biceps femoris, diaphragm and cardiac muscle. The present studies were designed to test for effects of chronically increased maternal cortisol on gene expression and metabolomics in placentomes near term. We hypothesized that changes in placenta may underlie or contribute to the alterations in fetal serum metabolomics, and thereby contribute to changes in striated muscle metabolism. Multi-omic analysis indicates that amino acid metabolism, particularly of branched chain amino acids and glutamate occur in placenta; changes in amino acid metabolism, degradation or biosynthesis in placenta were consistent changes in valine, isoleucine, leucine and glycine in fetal serum. The analysis also indicates changes in glycerophospholipid metabolism, and suggests changes in ER stress and antioxidant status in the placenta. These findings suggest that changes in placental function occurring with excess maternal cortisol in late gestation may contribute to metabolic dysfunction in the fetus at birth. Placentomes were collected from pregnancies in early labor (143±1 d gestation) of control ewes (n=7) or ewe treated with cortisol (1 mg/kg/d Solu-Cortef iv; n=5) starting at day 115 of gestation. Transcriptomics and metabolomics were performed using an ovine gene expression microarray (Agilent 019921), HR-MAS NMR respectively. Ewes carrying singleton sheep fetuses at 139-144d gestation (approximately term) were used.