Pineal melatonin improves bisphenol A-induced enterotoxicity via tryptophan/AhR/mitochondria signaling in pregnant mice.

Bisphenol A (BPA), recognized as an endocrine disruptor, is widely utilized in the manufacturing of various household products. Research has demonstrated that maternal exposure to BPA during pregnancy is associated with intestinal disorders and can adversely affect offspring. Furthermore, previous studies have identified that melatonin (MT), secreted by the pineal gland, plays a crucial role in maintaining intestinal health and exhibits detoxification properties. Therefore, this study investigates the therapeutic effects of MT on BPA-induced intestinal damage in pregnant mice. The findings indicate that BPA exposure compromises gut mucosal barrier function, evidenced by a reduction in the integrity and height of small intestinal villi, a decrease in goblet cell numbers, and diminished levels of MUC2 and tight junction proteins, alongside increased apoptosis, oxidative stress, and mitochondrial dysfunction. Additionally, BPA exposure significantly downregulated the levels of tryptophan-derived bacteria, tryptophan, and the aryl hydrocarbon receptor (AhR). Conversely, melatonin supplementation exerted beneficial effects on gut homeostasis, enhanced the gut mucosal barrier, and restored gut microbiota balance. Furthermore, in vitro experiments demonstrated that tryptophan can enhance mitophagy through the activation of the AhR, thereby improving intestinal barrier function in Caco-2 cells. In conclusion, our findings provide a novel theoretical foundation for the future application of melatonin in promoting intestinal health. They also offer innovative insights into the relationship between melatonin and the intestinal tryptophan/AhR/mitochondria axis, emphasizing its potential for enteroprotection against BPA-induced enterotoxicity.