The effect of prenatal nicotine on mRNA of central cholinergic markers and hematological parameters in rat fetuses

Abstract

A number of studies have demonstrated the influence of nicotine on fetal development. This study determined the expression of choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), and high-affinity choline transporter (CHT1) in the forebrain and hindbrain following chronic prenatal nicotine exposure in the rat fetus (maternal rats were subcutaneously injected with nicotine at different gestation periods). We also measured the effect of chronic nicotine exposure on fetal blood pO(2), pCO(2), pH, Na(+) and K(+) concentrations, as well as lactic acid levels. Maternal nicotine exposure during pregnancy was associated with a decrease in fetal pO(2) coupled with a significant increase in pCO(2) and lactic acid as well as restricted fetal growth. Additionally, maternal nicotine administration also reduced ChAT, VAChT, and CHT1 mRNA levels in the fetal brain. Nicotine-induced fetal hypoxic responses and reduced cholinergic marker expression in the brain were more severe when nicotine was started in early gestation. Our results provide new information about the effects of repeated exposure to nicotine in utero on the expression of central ChAT, VAChT, and CHT1 in the rat fetus. These results indicate that repeated hypoxic episodes or/and a direct effect of nicotine on the central cholinergic system during pregnancy may contribute to brain developmental problems in fetal origin.

Fig. 1

The effect of subcutaneous injection (s.c.) of nicotine in maternal rats on maternal blood pH, pCO₂, pO₂, O₂ saturation, Na⁺ and K⁺ levels and plasma osmolality, lactic acid levels. Control: the control animals; early: maternal s.c. nicotine from GD 3 to 21; middle: maternal s.c. nicotine from GD 9 to 21; late: maternal s.c. nicotine from GD 15 to 21.

Fig. 2

The effect of subcutaneous injection (s.c.) of nicotine in maternal rats on fetal blood pO₂, O₂ saturation. Control: the control animals; early: maternal s.c. nicotine from GD 3 to 21; middle: maternal s.c. nicotine from GD 9 to 21; late: maternal s.c. nicotine from GD 15 to 21. * and ^#p < 0.05; * vs. the Control; # vs. the late group.

Fig. 3

The effect of subcutaneous injection of nicotine in maternal rats on fetal blood PCO₂. Control: the control animals; early: maternal s.c. nicotine from GD 3 to 21; middle: maternal s.c. nicotine from GD 9 to 21; late: maternal s.c. nicotine from GD 15 to 21. * and ^#p < 0.05; * vs. the Control; # vs. the late group.

Fig. 4

The effect of subcutaneous injection of nicotine in maternal rats on fetal blood Na⁺ and K⁺ levels and plasma osmolality. Control: the control animals; early: maternal s.c. nicotine from GD 3 to 21; middle: maternal s.c. nicotine from GD 9 to 21; late: maternal s.c. nicotine from GD 15 to 21.

Fig. 5

The effect of subcutaneous injection of nicotine in maternal rats on fetal blood lactic acid levels. Control: the control animals; early: maternal s.c. nicotine from GD 3 to 21; middle: maternal s.c. nicotine from GD 9 to 21; late: maternal s.c. nicotine from GD 15 to 21. * and ^#p < 0.05; * vs. the Control; # vs. the late group.

Fig. 6

The effect of subcutaneous injection of nicotine in maternal rats on fetal blood pH. Control: the control animals; early: maternal s.c. nicotine from GD 3 to 21; middle: maternal s.c. nicotine from GD 9 to 21; late: maternal s.c. nicotine from GD 15 to 21.

Fig. 7

The effect of subcutaneous injection of nicotine in maternal rats on fetal body weight. Control: the control animals; early: maternal s.c. nicotine from GD 3 to 21; middle: maternal s.c. nicotine from GD 9 to 21; late: maternal s.c. nicotine from GD 15 to 21. * and ^#p<0.05; * vs. the Control; # vs. the late group.

Fig. 8

The effect of subcutaneous injection of nicotine in maternal rats on ChAT mRNA levels in the fetal forebrain (left) and hindbrain (right). Control: the control animals; early; maternal s.c. nicotine from GD 3 to 21; middle: maternal s.c. nicotine from GD 9 to 21; late: maternal s.c. nicotine from GD 15 to 21. * and ^#p < 0.05; * vs. the Control; # vs. the late group.

Fig. 9

The effect of subcutaneous injection of nicotine in maternal rats on VAChT and CHT1 mRNA levels in the fetal forebrain (left) and hindbrain (right). Control: the control animals; early: maternal s.c. nicotine from GD 3 to 21; middle: maternal s.c. nicotine from GD 9 to 21; late: maternal s.c. nicotine from GD 15 to 21. * and ^#p < 0.05; * vs. Control; # vs. late group.