ABSTRACT
Environmental chemicals and pollutants are increasingly recognized for their potential transgenerational effects. Acetyl tributyl citrate (ATBC), a widely used plasticizer substituting di-(2-ethylhexyl) phthalate (DEHP), was identified as an inducer of lipogenesis in male mice by our previous research. This study aimed to investigate the impact of ATBC exposure on the metabolic homeostasis of female mice and simultaneously evaluate its intergenerational effects. Female C57BL/6J mice were orally exposed to ATBC (0.01 or 1 µg/kg/day) for 10 weeks before mating with unexposed male mice. The resulting F1 female mice were bred with unexposed males to generate F2 offspring. Our results indicated that 10-week ATBC exposure disrupted glucose metabolism homeostasis and the reproductive system in F0 female mice. In F1 female mice, elevated liver lipid levels and mild insulin resistance were observed. In the F2 generation, maternal ATBC exposure resulted in increased weight gain, elevated liver triglycerides, and higher fasting blood glucose levels, primarily in F2 male mice. These findings suggest that maternal ATBC exposure may exert intergenerational disturbing effects on glucose metabolism across generations of mice. Further investigation is needed to evaluate the health risks associated with ATBC exposure.