Polystyrene microplastics-induced gut microbiota dysbiosis with altered short chain fatty acid is associated with reproductive physiology and endocrine disorder in female zebrafish

Microplastics (MPs) have emerged as critical disruptors of female reproduction, not only by direct toxicity but also via gut microbiota dysbiosis and short-chain fatty acid (SCFA) imbalance. This study explored the gut-SCFA-ovary axis, revealing that MPs-induced dysbiosis - similar to gentamicin model - enriches pathogens, depletes SCFA producers, elevates dysbiosis marker - gusβ and alters SCFA metabolites. These disruptions activate the gpr43 receptor, promoting systemic inflammation, leaky gut and endotoxin translocation. Consequent metabolic shifts (low leptin & high ghrelin) mimic an energy-deficient state, which the brain interprets as unsuitable for reproduction, suppressing the HPG axis. This leads to reduced kisspeptin-1, GnRH, LH, FSH, β-estradiol, testosterone, and vitellogenin, impairing steroidogenesis, folliculogenesis, and ovulation, confirmed by histology and decreased %GSI. MPs further activate ovarian TLR4α- nf-κb signaling, driving oxidative stress and inflammation, while fads2-elovl2 suppression limits ω-3 PUFA synthesis, damaging oocyte membrane dynamics and accelerating atresia causing micropore formation, as shown by SEM. Collectively, these findings provide the first evidence that MPs-induced gut microbiota dysbiosis critically mediates female reproductive impairments through immune-metabolic endocrine crosstalk, highlighting the need to preserve microbiota to mitigate reproductive toxicity.