Prenatal hypoxia impairs circadian synchronisation and response of the biological clock to light in adult rats.

The aim of this study was to test the hypothesis that prenatal hypoxia in rats might lead to consistent changes in the entrainment of the circadian clock by light. Pregnant female rats were placed in a chamber provided with hypoxic gas (10 % O2--90 % N2) at gestational day 5 and returned to normoxia before delivery. Once adult, rats born to hypoxic mothers had significant alterations in their circadian rhythm of locomotor activity (recorded in freely accessible running wheels). Under a regular 12/12 light/dark (LD) cycle, they showed a phase advance of their rhythm of activity (mean phase advance of 87 min) and were less active than control rats. After an abrupt 6 h phase delay in the LD cycle, rats from the prenatal hypoxic group (PNH) took significantly more time to resynchronise to the new LD cycle compared to controls (+53 %; 6.0 +/- 1.5 vs. 9.2 +/- 0.5 days respectively). Under constant darkness, PNH and control rats had a similar period of activity (24.27 +/- 0.20 vs. 24.40 +/- 0.13) but the response of PNH rats to a light pulse in the early subjective night was less marked than that of control rats (101 +/- 9 vs. 158 +/- 13 min). When submitted to acute restraint stress, PNH rats had a prolonged secretion of corticosterone compared to controls. These results indicate that prenatal hypoxia is a factor that has long lasting consequences for the functional output of the biological clock and the hormonal response to stress.