CHANGES IN PLASMA ADENOSINE DURING SIMULATED BIRTH OF FETAL SHEEP

Adenosine is known to inhibit nonshivering thermogenesis in adult brown fat. These experiments were undertaken to test whether fetal adenosine, normally present in high concentrations, suppresses lipolysis in utero and then falls after birth, permitting thermogenesis to begin. To test this hypothesis, we measured fetal plasma adenosine concentration [ADO] using high-performance liquid chromatography in 11 fetal sheep at 135-140 days gestation during simulated birth. During an initial control period, fetal [ADO] averaged 1.9 +/- 0.3-mu-M, about four times maternal [ADO] (0.4 +/- 0.1-mu-M, P < 0.001). The fetus was then cooled by circulating cold water through a plastic coil encircled about the fetal torso. One hour later, when fetal core temperature had decreased 2.3-degrees-C, fetal [ADO] averaged 2.8 +/- 0.5-mu-M, a 50% increase (P < 0.05), while thermogenesis remained inactive. Next the fetal lungs were ventilated with O2 to raise arterial Po2 to greater-than-or-equal-to 150 Torr. Fetal [ADO] decreased only slightly, and thermogenic responses were modest. Finally, the umbilical cord was occluded. Fetal [ADO] decreased rapidly and 60 min later averaged 1.1 +/- 0.2-mu-M, 40% below initial control (P < 0.05) and 57% below the previous period (P < 0.001). As [ADO] fell, strong thermogenic responses became apparent, as indicated by seven- to eightfold increases in plasma glycerol (P < 0.001) and a doubling in fetal O2 consumption (P < 0.001). These results are consistent with the hypothesis that high fetal [ADO] inhibits thermogenesis before birth but then decreases after cord occlusion, allowing thermogenesis to begin. The results also suggest that circulating fetal adenosine is derived in part from the placenta or fetal liver and permit the speculation that adenosine plays a critical role in regulating fetal metabolism.