Fucoxanthin Attenuates Bisphenol A-Induced Testicular Injury via NF-κB-Mediated Pyroptosis Inhibition.

Background: Bisphenol A (BPA), a widely used industrial chemical, is a well-known endocrine disruptor linked to testicular damage and impaired male reproductive function. Fucoxanthin (Fx), a marine carotenoid with potent antioxidant properties, has not been extensively studied for its potential to mitigate BPA-induced testicular injury. Aims: To evaluate the protective effects of Fx against BPA-induced testicular injury and explored the underlying signaling mechanisms. Study Design: Experimental study. Methods: A mouse model of BPA-induced testicular injury was established. Transcriptomic analysis was performed to identify significantly altered genes. The therapeutic potential of Fx was assessed using combined molecular and histological approaches. Complementary Results: Fx administration markedly attenuated BPA-induced disruptions in serum sex hormones, testicular histopathology, and proinflammatory cytokine levels. Ribonucleic acid sequencing revealed that Fx's protective effects are associated with modulation of the nuclear factor kappa B (NF-κB), nucleotide-binding oligomerization domain-like, and Toll-like receptor signaling pathways. Validation experiments indicated that Fx inhibits nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and suppresses pyroptosis, accompanied by downregulation of key genes and proteins in the lipopolysaccharide/NLRP3 signaling cascade. Conclusion: These findings suggest that Fx may serve as a promising dietary supplement or nutraceutical agent to mitigate the adverse reproductive effects of environmental endocrine disruptors, with potential benefits for male reproductive health.