Exposição de ratas Wistar ao tributilestanho durante a gestação e a lactação: efeitos sobre a prole recém-desmamada e adolescente de ambos os sexos

Abstract

Tributyltin (TBT), an organotin compound, widely used as a biocide in boat paints, has been highlighted as an important endocrine disruptor. The leaching of this substance increases water and food contamination, especially marine fish. Studies have shown that exposure to TBT, even at low doses, can induce obesity, infertility and metabolic dysfunctions. However, the relationship between exposure to TBT during pregnancy and lactation, considered critical windows for metabolic programming, as well as the short- and long-term effects are not yet elucidated. Our hypothesis is that the offspring of mothers exposed to TBT during critical stages of development may present endocrine-metabolic dysfunctions in the early stages of their development, as a short-term effect. For this purpose, we used pregnant Wistar rats randomly divided into the following groups: Control, which received a vehicle solution (ethanol 0.01%); TBT 100ng, which received TBT at a dose of 100ng/kg bw/day; and TBT 1000ng, which received TBT at a dose of 1000ng/kg bw/day. The respective solution were administered by intragastric gavage from the gestational day 7 (GD7) to lactational day 21 (LD21). Biometric and biochemical parameters of the mothers were evaluated at the end of lactation. Offspring of both sexes were evaluated at birth, weaning (21 days old) and adolescence (45 days old). Exposure to TBT does not program changes in body weight, food consumption, glycemic and lipid profile of mothers. However, it promotes specific and dose-dependent changes in mothers, such as increased total fat mass at delivery (TBT 100ng), reduction in gonadal and mesenteric fat depots at the end of lactation (TBT 1000ng) and changes in milk composition, such as increased protein and total cholesterol content, with reduction in lactose (TBT 100ng). In female offspring, TBT promotes low birth weight (TBT 100ng), a reduction in naso-anal length and an increase in blood glucose (TBT 1000ng), with no changes in males. At weaning, female offspring (TBT 1000ng) has reduced retroperitoneal fat depots, uterine weight and serum leptin levels (both doses). In adolescence, male offspring shows reduced lean mass (TBT 1000ng) and increased prostate weight (TBT 100ng), with no changes in females. In summary, maternal exposure to TBT at low doses induces dose, sex, age and tissue-specific alterations and seems to be more harmful to female offspring. These changes suggest that these animals should exhibit, in adulthood, a higher risk of developing obesity and associated diseases.