EFFECTS OF MATERNAL INTAKE OF NICOTINE ON FETAL AND NEWBORN RATS.

Abstract

Administration of nicotine to pregnant animals has been shown to produce capillary damage in the placenta in dogs(l), skeletal defects of the offspring and decrease of litter size in mice(2), vertebral anomalies in chicks (3), and postponement of the appearance of the first litter(4) and lighter weight offspring in rats(5). Administration of nicotine to nursing rat mothers is associated with a poor neonatal weight gain(5) and an increase in neonatal mortality (5,6). Geller(7) gave pregnant rats nicotine doses less than 15% of those used by Nishimura and Nakai in mice (2) and produced no fetal abnormalities. This difference may be explained on the basis of dosage and species differences; however, the current status of this problem is unsettled. Acute administration of nicotine results in a rise in serum free fatty acids in dogs and humans(8). Smokers, when compared with non-smokers, have been shown to have increased serum lipoproteins(9) and cholesterol (9,10,11) and to produce babies of lighter weight (12). The effect of nicotine on fetal lipids has not been investigated. In this study, a nicotine solution in place of water was given to rats throughout pregnancy and up to the time of weaning in order to determine its effect on fetal and neonatal growth and mortality. Measurements of neonatal brain and liver lipid and cholesterol content were made as a preliminary investigation of the effect of nicotine on fetal lipid metabolism. Materials and methods. Two experiments were carried out using virgin Sprague-Dawley female rats which were mated to males of the same strain. The body weight at the start of pregnancy ranged from 237 to 305 g. Conception was dated from the time of the appearance of the vaginal plug. The experimental groups were given a solution of .05 mg/ml nicotine as the sole source of drinking water from time of conception throughout pregnancy and the control animals were given distilled water. The solution and water were given ad libin graduated drinking tubes and daily intake was recorded. All animals were given Purina Lab Chow ad lib. In Experiment I, 8 rats given nicotine and 9 control rats were studied. Three of the experimental animals received nicotine only for the last 14 days, 6 days and 4 days of pregnancy respectively. Within a few hours of birth the newborn rats were weighed and then killed by decapitation. The brains and livers were promptly dissected free of other tissue, weighed, and frozen. Lipid and nitrogen determinations were performed on pooled brains and livers for each litter. The tissues were homogenized with 50 ml of 2:1 chloro-form-methanol per g of tissue in a micro Waring blendor. An aliquot of uniformly mixed tissue homogenate was removed for nitrogen analysis. The remainder was centri-fuged; the supernatant was left in contact with distilled water overnight and total lipid and cholesterol were then determined. The mother rats were killed at the time of the dissections of the neonates in order to determine the number of uterine patches and absorbing fetuses. In Experiment II, 8 rats were given the nicotine solution, with 5 controls. After the litters were delivered the nicotine group remained on the nicotine solution. All the young and maternal animals were killed with ether 21 to 22 days after delivery. Only body weight was recorded. Results. Newborn rat (Exp. I). Nicotine intake. Five nicotine and 5 control females had daily intake records for the entire period of gestation. Average intake of water by the controls was 125 ml/kg/day. Average intake of nicotine solution was 53 ml/kg/day or the equivalent of 2.7 mg nicotine/kg/day. The body weight used in the calculation was the 10th day weight interpolated from the weekly body weight measurements. Maternal weight gain. All rats showed a weight gain during pregnancy. One nicotine female had only one weight recorded. The other nicotine rats showed weight curves comparable to the controls in slope.