ORIGINAL ABSTRACT

Glyphosate-based herbicide (GBH) exposure during critical life development periods can interfere with hormonal and metabolic regulation. Puberty may be particularly vulnerable to such disruptions, leading to long-term health consequences. However, whether GBH exposure limited to puberty increases susceptibility to obesity and its comorbidities in adulthood remains poorly understood. So, we investigated the effects of pubertal exposure to GBH on glucose and lipid homeostasis, as well as on sex, thyroid, and cortisol hormone levels, in male and female mice subjected to a high-fat diet (HFD) in adulthood. From 30 to 60 days of age, male and female C57Bl/6 mice received a daily gavage of either distilled water [control (CTL group)] or 50 mg/kg of GBH (GBH group). Following this period until 150 days old, CTL and GBH female and male were fed on a HFD. GBH-exposed females showed exacerbated HFD-induced increases in body weight, abdominal adiposity, and hyperphagia. However, the hypothalamic mRNA expression of the neuropeptides Agrp, Cart, and Pomc remained unaltered. GBH exposure did not change HFD effects on glucose homeostasis between OB-GBH and OB-CTL groups. In both sexes, GBH exposure aggravated HFD-induced hepatic steatosis. These effects were accompanied by elevated plasma levels of T3 and cortisol in OB-GBH groups, along with increased testosterone and estradiol levels in OB-GBH males and females, respectively. GBH exposure restricted to the pubertal period led to increased ectopic fat accumulation in the liver and dysregulation of T3, cortisol, and sex hormone levels in female and male mice exposed to an obesogenic challenge.