Withdrawal of placental prostaglandins permits thermogenic responses in fetal sheep brown adipose tissue

Abstract

Significant nonshivering thermogenesis cannot be demonstrated in fetal sheep cooled in utero but can be induced by supplemental oxygenation and umbilical cord occlusion, which suggests the presence of inhibitor(s) of placental origin. To test the hypothesis that an ecosanoid could be such an inhibitor, we studied eight fetal sheep at 136-141 days gestation. Thermistors were placed in the fetal esophagus, a cooling tube was placed around the trunk, a tracheal cannula and carotid catheters were inserted, and a snare was placed loosely around the umbilical cord. After indomethacin infusion for 18 h, the fetuses were cooled by 2.13 +/- 0.13 degrees C by circulating cold water through the coil. Within 60 min plasma free fatty acid levels rose threefold to 245 +/- 82 mu eq/l (P < 0.01) and glycerol levels rose to 197 +/- 17 mumol/l (P < 0.01). Ventilation caused a further rise in thermogenic indexes, and fetal oxygen consumption rose to 19.9 +/- 1.2 ml.kg-1.min-1. In four fetuses we ceased cooling, which caused thermogenic indexes to fall and oxygen consumption to fall to 6.9 +/- 1.1 ml.kg-1.min-1. We continued to cool three fetuses and infused prostaglandin E2 into the fetuses for 60 min; thermogenic indexes and oxygen consumption fell rapidly on infusion and rose rapidly when infusion ceased. We suggest that placental prostaglandins inhibit brown adipose tissue thermogenesis before birth and that withdrawal after placental separation is one factor in the initiation of nonshivering thermogenesis at birth.