Prenatal hypoxia impairs the postnatal development of neural and functional chemoafferent pathway in rat

Abstract

1. To define the effects of prenatal hypoxia on the postnatal development of the chemoafferent pathway, ventilation and metabolism, pregnant rats were exposed to normobaric hypoxia (10 % oxygen) from embryonic day 5 to embryonic day 20. Offspring were studied at 1, 3 and 9 weeks of age in three separate protocols. 2. Prenatal hypoxia decreased the dopamine content in the carotid bodies at all ages, and decreased the utilisation rate of noradrenaline in the caudal part of the A2 (A2c), A1 and A5 noradrenergic brainstem cell groups at 3 weeks after birth. At 9 weeks of age, the level of dopamine in the carotid bodies was still reduced but the utilisation rate of noradrenaline was enhanced in A1. 3. Rats from dams subjected to hypoxia during pregnancy hyperventilated until 3 weeks after birth. In these rats, the biphasic hypoxic ventilatory response was absent at 1 week and the increase in minute ventilation was amplified at 3 weeks. 4. Prenatal hypoxia disturbed the metabolism of offspring until 3 weeks after birth. A weak or absent hypometabolism in response to hypoxia was observed in these rats in contrast to control animals. 5. Prenatal hypoxia impairs the postnatal development of the chemoafferent pathway, as well as the ventilatory and metabolic responses to hypoxia. These alterations were mostly evident until 3 weeks after birth.

Figure 1. Schematic diagram illustrating the location of the punched areas

Each number (from -1 to 11) represents a consecutive slice of 480 μm coronal section. Each slice is numbered according to its position relative to that containing the pyramidal decussation (referred to as 0). The caudal part of the A₂ cell group is punched out from 3 slices (-1 to 1). The A₁ cell group is punched out from 5 slices (0-4) and the A₅ cell group from 3 slices (8-10).

Figure 2. Effect of prenatal hypoxia on noradrenaline utilisation rate in brainstem cell groups of 3- and 9-week-old rats

Bars represent means ±s.e.m. of noradrenaline utilisation rate in the different brainstem cell groups (A₂c, A₁ and A₅) from control rats (Cont) at 3 (n = 24) and 9 (n = 24) weeks of age, and rats at 3 (n = 21) and 9 (n = 23) weeks of age from dams subjected to hypoxia during pregnancy (Hypo). *P < 0.05, significant difference between Cont and Hypo group.

Figure 3. Integrated minute ventilation

Each graph shows data from a typical animal and represents the minute ventilation integrated breath by breath in a 1-week-old control rat (Cont; top) and in a 1-week-old rat from a dam subjected to hypoxia during pregnancy (Hypo; bottom). Thirty-one consecutive breath cycles are represented and numbered 1–29. Note the irregular ventilation in the Hypo rat compared with the Cont rat. Coefficients of variation in the Cont and Hypo group of rats are 0.24 ± 0.04 and 0.35 ± 0.02, respectively.

Figure 4. Effect of prenatal hypoxia on the amplitude of the hypoxic ventilatory response to 10 % O₂ hypoxia of 1-, 3- and 9-week-old rats

Graphs represent means ±s.e.m. of the differences between resting values and the data obtained during the hypoxic test, after 1, 4, 7 and 10 min of exposure, and therefore represent the response amplitude. Open triangles represent data obtained from rats from dams placed under hypoxia during pregnancy (Hypo) and filled squares represent data obtained from the control group of rats (Cont). In each graph: the left panel represents 1-week-old rats, the middle panel 3-week-old rats and the right panel 9-week-old rats. †P < 0.05, significant difference between hypoxic data and normoxic data within Cont or Hypo group; ‡P < 0.05, significant difference between hypoxic values at 4, 7 and 10 min compared with 1 min; *P < 0.05, significant difference between Cont and Hypo group; §P < 0.05, significant difference between data of 1- or 9-week-old rats compared with data of 3-week-old rats.

Figure 5. Effect of prenatal hypoxia on metabolism in resting conditions and during a 10 % O₂ hypoxic test of 1-, 3- and 9-week-old rats

The graph represents means ±s.e.m. of metabolic data obtained in resting conditions (time 0) and in hypoxic conditions (10 % O₂-90 % N₂) for 12 min. The graph on the left represents 1-week-old rats (Cont, n = 8; Hypo, n = 7), the middle graph 3-week-old rats (Cont, n = 6; Hypo, n = 10) and the right graph 9-week-old rats (Cont, n = 8; Hypo, n = 8). ▵, rats from dams placed in hypoxia during pregnancy (Hypo); ▪, control animals (Cont). *P < 0.05, significant difference between Cont and Hypo group.