Perfluorooctanoic acid induces transgenerational modifications in reproduction, metabolism, locomotor activity, and sleep behavior in Drosophila melanogaster and deleterious effects in human cancer cells

Perfluorooctanoic acid (PFOA) has been widely documented to affect various aspects of health, including development, metabolism and neuronal function in a variety of organisms. Despite numerous reports detailing these effects, a comprehensive mechanistic model remains elusive, especially with regard to the long-term effects of PFOA, as it bioaccumulates in food chains with a long half-life. In this study, we evaluated the impact of PFOA on several critical physiological states of Drosophila melanogaster. Our findings indicate that PFOA exposure significantly decreases reproductive capacity and induces alterations in starvation resistance and feeding behavior in flies. Interestingly, PFOA exposure also caused changes in locomotor activity and sleep patterns compared with flies receiving a standard diet. Notably, compared with controls, the F2 generation showed increased locomotion and shorter sleep duration during the dark phase, even without direct exposure to PFOA, indicating possible transgenerational effects. Transcriptomic analysis revealed that PFOA also disrupts fatty acid metabolism and alters the expression of immune-responsive genes in Drosophila. In the U-2 OS human osteosarcoma cell line, we examined the impact of PFOA on circadian rhythm regulatory proteins and discovered that, compared with controls, BMAL1 levels increased at concentrations from 10 nM to 10 μM. In summary, this research highlights the influence of PFOA on diverse biological processes, including reproduction, feeding behavior, starvation resistance, locomotion, and sleep activity in Drosophila. It also highlights the ability of PFOA to alter BMAL1 expression patterns in human osteosarcoma cells with deleterious effects.