Disfunções endócrinas no modelo de programação pela exposição à fumaça de cigarro na lactação

Abstract

Events or stimuli during early life can affect the development; among these events, there is the maternal smoking. Children born from smoking mothers showed low birth body weight and overweight in childhood and adolescence. Maternal nicotine exposure, the main cigarette component, causes in the offspring several metabolic changes in short- and long-term, such as increase in adiposity, hyperleptinemia, leptin resistance as well as thyroid and adrenal dysfunction. However, it is known that there are other toxic components in tobacco smoke. Then, we compared the effects of two models of tobacco smoke exposure on endocrine-metabolic profile in offspring at short- and long-term. For this, in the 3rd day of birth, suckling rats were submitted to two different experiments: Model I (through breast milk exposure), in which litters were separated into, smoke exposure (SE; n=8) lactating mothers exposed to 2R1F cigarettes smoke (1.7 mg nicotine/cigarette/1h, 4 times per day) separated from their offspring; and control (C; n=8) mothers were separated of their pups and exposed to filtered air. Model II (direct exposure), in which litters were separated into: Smoke exposure (SE; n=8) lactating mothers and their offspring were exposed to 2R1F cigarettes smoke; and control (C; n=8) mothers and their pups were exposed to filtered air. The smoke exposure occurred until the weaning, when mothers and half of pups were killed. The other offspring were killed at 180 days-old. SE dams presented hypoleptinemia (-46%), hyperprolactinemia (+50%), hypoinsulinemia (-40%) and lower triglycerides (-53%). Concerning milk compositon, SE dams showed higher lactose (+52%) and triglycerides (+78%). In model I (through breast milk exposure), EF offspring showed at weaning lower total body fat (-24%) and higher total body protein (+17), lower serum glucose (-11%), hyperinsulinemia (+28%), hypocorticosteronemia (-40%) and higher triglycerides (+34%). In adulthood, these parameters were normalized, except for the adrenal function, featured by lower catecholamines content (-50%) and tyrosine hydroxylase expression in adrenal medulla (-56%). In model II (direct exposure), SE offspring (21 days-old) presented lower BW (-7%) and length (-5%), VFM (-28%) and visceral adipocytes area (-60%) with higher subcutaneous adipocytes area (+95%), higher T4 (+59%), corticosterone (+60%) and adrenal catecholamines content (+58%) and lower serum insulin (-29%). At 180 days-old, SE offspring presented higher food intake (+10%) without change in BW, higher visceral fat depots (~60) and total body fat (+50%), lower subcutaneous adipocytes area (-24%), higher serum glucose (+11%), adiponectin (+1.4x), leptin (+85%), T3 (+71%), T4 (+57%), TSH (+36.5%), lower corticosterone (-41%) and adrenal catecholamines content (-57%) and higher triglycerides (+65%). Therefore, our data evidences the negative impact that exposure to cigarette smoke can have on the development of the neonate as well as on future endocrine disorders, which occur at least in part due to the changes observed in the mothers. Therefore, independent of the kind of exposure, i.e. through breastfeeding or direct inhalation, it is of great importance warn society about the long-lasting metabolic complications resulting from involuntary exposure of newborn to smoking.