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Here, adult female zebrafish were exposed to polystyrene nanoplastics (NPs; 80\u2009nm; 1.0\u2009mg\/L) for 21\u2009days, with or without moderate aerobic exercise (AE; 12\u2009cm\/s, 20\u2009min\/day). NPs exposure alone caused significant ovarian accumulation of particle\u2010like structures (TEM), elevated oxidative stress, increased follicular apoptosis (TUNEL), and disrupted reproductive hormones (E2, FSH, LH). It also induced anxiety\u2010 and depression\u2010like behaviors in novel tank and shoaling tests, accompanied by elevated cortisol and altered monoamine (NE, 5\u2010HIAA) levels. In contrast, concurrent AE markedly attenuated these effects: it reduced ovarian particle burden, improved antioxidant enzyme activities (SOD, POD), restored ovarian histoarchitecture, and normalized endocrine and neuroendocrine measures. These changes were supported by partial recovery of ovarian (ESR1,\n                    <jats:italic>cyp19a1a<\/jats:italic>\n                    , AMH) and brain (BDNF, TPH2) transcript levels. Gut microbiome profiling revealed that AE counteracted NPs\u2010associated dysbiosis, enriching beneficial taxa, including\n                    <jats:italic>Akkermansia<\/jats:italic>\n                    and Lachnospiraceae_NK4A136_group. Predictive functional inference and correlation analyses linked these microbial shifts to enhanced fatty acid and tryptophan metabolic potential, which correlated with neuroendocrine recovery. Together, these data support a working model in which AE acts as an exposure modifier, coupling host physiology and microbiome\u2010associated metabolic capacity to mitigate NPs\u2010induced neuroendocrine dysfunction via a gut\u2013ovary\u2013brain continuum. Targeted metabolomics and causal microbiota perturbation will be needed to validate specific mediators.\n                  <\/jats:p>","DOI":"10.1096\/fj.202600941r","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T08:02:16Z","timestamp":1779264136000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Lifestyle Modulation of Xenobiotic Stress: Aerobic Exercise Attenuates Nanoplastic\u2010Associated Neuroendocrine Dysfunction via a Gut\u2013Ovary\u2013Brain Continuum"],"prefix":"10.1096","volume":"40","author":[{"given":"Huaibiao","family":"Xu","sequence":"first","affiliation":[{"name":"Institute of Life Sciences &amp; Biomedical Collaborative Innovation Center of Zhejiang Province Wenzhou University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bofei","family":"Xu","sequence":"additional","affiliation":[{"name":"National Engineering Research 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