Perinatal exposure of C57Bl/6 mice to ametryn and metabolic outcomes in adulthood
obesity; endocrine disruptors; environmental obesogens; adipose tissue
“In recent years, evidence has accumulated regarding the role of environmental contaminants in the development of obesity and its metabolic complications. These substances, known as endocrine disruptors (EDs) or metabolic disruptors, are widely used in industrial and agricultural activities and have the ability to interfere with different aspects of energy homeostasis, thereby affecting bodyweight regulation and glucose metabolism. The present study aimed to investigate the effects of perinatal exposure to the pesticide ametryn on metabolic outcomes in adulthood in mice. Female C57BL/6 mice (parental generation) were exposed to ametryn through drinking water, starting one week before mating, suspended during mating, and resumed after this period, continuing throughout gestation and lactation. The concentration used (50 ng/mL) was selected based on environmental levels previously described in the literature. The offspring (F1 generation) were allocated into four experimental groups for each sex: perinatal exposure to control + normolipidic diet in adulthood; perinatal exposure to control + high-fat diet in adulthood; perinatal exposure to ametryn + normolipidic diet in adulthood; and perinatal exposure to ametryn + high-fat diet in adulthood. The normolipidic diet consisted of 10% of caloric content from lipids, while the high-fat diet consisted of 30% of caloric content from lipids. The offspring were monitored for body weight and evaluated for glucose tolerance using a glucose tolerance test, and for insulin sensitivity using an insulin tolerance test. It was observed that males exposed to ametryn exhibited increased weight gain in adulthood, which was intensified by high-fat diet consumption. In females fed a normolipidic diet, ametryn exposure did not influence adult weight gain; however, it did promote increased weight gain in those fed a high-fat diet. A similar pattern was observed for glucose tolerance: males exposed to ametryn showed impaired glucose tolerance regardless of diet, and females exhibited impaired glucose tolerance when fed a high-fat diet, but not when fed a normolipidic diet. No significant changes in insulin sensitivity were observed. The results of this study indicate that, in the murine model used, ametryn exhibits characteristics consistent with the action of an obesogenic agent in vivo, with its effects being amplified by concomitant exposure to a high-fat diet. These findings strengthen the relevance of ametryn as a potential modulator of metabolic pathways related to adiposity accumulation. However, additional investigations—including mechanistic analyses and assessments in different experimental models—are essential to clarify the underlying processes and further substantiate the observed effects. ”