ABSTRACT
OBJECTIVE To investigate the transgenerational effect of neuroendocrine metabolic programmed alteration in adult intrauterine growth retardation (lUGR) offspring rats with prenatal nicotine exposure. METHODS Pregnant Wistar rats were administered daily with nicotine (2 mg.kg-1 ) by sc from gestational day 11 until delivery. F1 offspring was fed with a standard diet before four groups in F2 were set up according to the cross-mating between F1 normal adult rats and nicotine-induced lUGR adult rats. CC group was mated by F1 normal adult rats, CN group by F1 normal adult male rats and lUGR adult female rats, NC group by F1 lUGR adult male rats and normal adult female rats, while NN group was mated by F1 lUGR adult rats. F2 adult rats were subjected to a fortnight ice water swimming stimulus. Blood samples were collected before and after stress and then detected for the levels of adrenocortico-tropic hormone ( ACTH), corticosterone ( CORT), glucose, triglycerides ( TG) and total cholesterol (TCH). RESULTS Before stress, the level of serum CORT in F2 male rats of NN group was decreased to 73.9% of that of the CC group (P<0.05),while the level of serum TG in F2 male rats of CN and NC groups was increased to 1.43 and 1.52 times that of the CC group, respectively ( P<0.05). Meanwhile, the level of serum TG in F2 female rats of CN, NC and NN groups was increased to 1.71, 1.80 and 1.81 times that of the CC group, respectively (P<0.05). After stress, the serum CORT gain rate in F2 male rats of CC group was -1.67%, but was 36.0% in NN group. The serum glucose level in male NC group and in female CN group was increased to 1.61 and 1.62 times that of the corresponded CC groups, respectively (P<0.01). Furthermore, the serum TG gain rate in F2 rats of each nicotine group was decreased markedly in comparison with their corresponding controls (P<0.05), ie, the serum TG gain rates in F2 male rats of CN, NC and NN groups were decreased to 46.4%, 16.7% and 7.7% of the CC group, while the serum TG gain rates in F2 female rats of these groups were decreased to 20.6%, 4.0% and 8.4% of the CC group, respectively. Compared with CC group, TCH level of females and males in NN group was decreased by 40.5% and 21.9%(P<0.01) before stress, respectively, and the TCH gain rate of females in NN group was increased by 49.7%(P<0.05) after stress. CONCLUSION The reproductive and developmental toxicities and the neuroendocrine metabolic programming alterations induced by prenatal nicotine exposure are transgenerated to F2 offspring and these effects exhibit gender and parental differences.