Effects of sustained hypoxaemia with 72 hours recovery on 11 beta-hydroxysteroid dehydrogenase types 1 and 2 gene expression in near-term fetal sheep

Abstract

The study examined the effects of 8 h sustained hypoxaemia, with 72 hrecovery, on the expression of 11 beta-hydroxysteroid dehydrogenase (11b-HSD) types 1 and 2 in near-term fetal sheep. Placental tissue and fetal liver andkidney were collected at Days 135-138 gestation 72 h after 8 h sustained hypoxaemia induced by lowering maternal inspired oxygen with(n= 9) and without (n= 6) metabolic acidosis or after 8 h normoxia (n= 6). In hypoxic fetuses with metabolic acidosis, a significantincrease in the level of 11 beta-HSD2 mRNA in the kidney compared with controls was correlated significantly with degree of associated fetal acidaemia, but there were no corresponding increases in the tissue level of 11 beta-HSD2 activity. Hence, a time lag may exist between the mRNA and activity. Alternatively, the translation of 11 beta-HSD2 mRNA may be inhibited. In contrast, levels of 11 beta-HSD1 mRNA in the placenta and fetal liver were unchanged 72 h after sustained hypoxaemia. These results indicate that sustained fetal hypoxaemia with metabolic acidosis selectively up-regulates 11 beta-HSD2 mRNA expression in the near-term fetal sheep kidney.This may be a re-bound effect at 72 h following an initial down-regulation as observed in a previous study.