Prepregnancy Exposure to High Doses of Nanoplastics Triggers Persistent Vaginal Microbiome Dysbiosis to Induce Adverse Pregnant Outcomes

Abstract The global accumulation of nanoplastics poses wide concerns for human health. Although their toxicity in various organs is being uncovered, their impact on vaginal microbiomes that are essential for healthy reproduction remains largely unknown. Here, we discover a previously unrecognized long-term nanoplastic reproductive toxicity that prepregnant exposure to high doses of aged polystyrene nanoparticles (aPS-NPs) induces mouse miscarriage and restricts embryo development by persistently causing vaginal microbial dysbiosis (an increase in Aerococcus urinae abundance), vaginal glutamine depletion (suppression of Slc1a5-mediated import of glutamine from outside cells to intracells), and vaginal inflammation (up-regulation of Ifnar1, Il-1β, and Il-18) from prepregnancy to pregnancy, despite the fact that aPS-NPs are almost undetectable in the vagina on D14 in pregnancy. Transplant of A. urinae into the vaginal tract exacerbates these processes and adverse pregnancy outcomes. Interventions, such as Slc1a5 overexpression, glutamine supplement, or anti-inflammatory treatment, can effectively recover these processes and alleviate the adverse outcomes. Therefore, this study not only demonstrates a previously unrecognized long-term nanoplastic reproductive toxicity by persistently causing vaginal dysbiosis, metabolic dysfunctions, and inflammation, ultimately inducing adverse pregnant outcomes, but also provides experimental basis for targeted therapies to combat the escalating threat of nanoplastic pollution.