Polystyrene microplastics disrupt female reproductive health and fertility via sirt1 modulation in zebrafish (Danio rerio)

Microplastics (MPs) pollution poses an emerging threat to aquatic biota, which could hinder their physiological processes. Recently various evidence has demonstrated the toxic impacts of MPs on cellular and organismal levels, but still, the underlying molecular mechanism behind their toxicity remains ambiguous. The hypothalamic-pituitary-gonadal (HPG) axis regulates the synthesis and release of sex steroid hormones, and SIRT1 plays a vital role in this process. The current study aimed to elucidate the harmful effects of MPs on female reproduction via SIRT1 modulation. Healthy female zebrafish were exposed to different concentrations (50 and 500 µg/L) of polystyrene microplastics (PS-MPs). The results revealed a significant change in the gonadosomatic index (GSI) after exposure to PS-MPs. In addition, the decreased fecundity rate displayed an evident dosage effect, indicating that exposure to PS-MPs causes deleterious effects on fertilization. Furthermore, significantly enhanced levels of reactive oxygen species (ROS) and apoptotic signals through the TUNEL assay were evaluated in different treated groups. Moreover, morphological alterations in the gonads of zebrafish exposed to MPs were also observed through H&E staining. The subsequent change in plasma steroid hormone levels (E2/T ratio) showed an imbalance in hormonal homeostasis. Meanwhile, to follow PS-MPs' effects on the HPG axis via SIRT1 modulation and gene expression related to steroidogenesis, SIRT1/p53 pathway was evaluated through qPCR. The altered transcription levels of genes indicated the plausible interference of PS-MPs on the HPG axis function. Our in-silico molecular docking study proves that PS-MPs efficiently bind and inhibit endocrine receptors and SIRT1. Thus, these findings add to our understanding of the probable molecular mechanisms of reproductive impairment caused by PS-MPs in zebrafish.