Gut-ovary axis mediated synergistic reproductive toxicity of polystyrene nanoplastics and perfluorobutanoic acid co-exposure: pyroptotic signaling and probiotic mitigation

Abstract Polystyrene nanoplastics (PS-NPLs) and perfluorobutanoic acid (PFBA) are pervasive contaminants of great concern and can enter human body primarily through gastrointestinal tract. However, their single and combined effects on female reproductive health remain poorly explored. In this study, PFBA was found to be adsorbed onto PS-NPLs through both chemical and physical interactions. Compared with single exposure, co-exposure to PS-NPLs (0.04 mg/d) and PFBA (0.28 mg/d) for 28 days caused more severe ovarian toxicity in rats, as evidenced by decreased primordial follicles, increased follicular atresia, and sex hormone abnormalities. Mechanistically, the co-exposure was associated with the gut barrier damage and elevated levels of lipopolysaccharide in the bloodstream, concomitant with altered redox homeostasis, inflammation and NLRP3/caspase-1-related pyroptosis of the ovary. Moreover, supplementation with probiotic Lactiplantibacillus plantarum P101 partially attenuated ovarian injury via modulating gut microbiota and mitigating the above process. Taken together, our study revealed a synergistic impact of PS-NPLs and PFBA on female reproduction, uncovered the underlying mechanisms from the perspective of gut-ovary axis, and provided valuable insights into potential preventive strategies.