Low-dose exposure to microplastics retards meiotic maturation via HDACs insufficiency

Microplastics (MPs) are considered as one of the main reasons for male and female infertility. However, the reproductive toxicity and its related mechanisms are understood by animal models with acute exposure to MPs at present. In the study, we show the low-dose polystyrene microplastics (PSMPs) exposure results in severely abnormal reproduction in female, but not male in mouse model, exhibiting failed oocyte meiotic maturation. Mechanistically, the PSMPs exposure induces the over-activation of cell metabolism pathways, insufficient HDACs and H4K16 hyperacetylation in oocytes in vivo and in vitro. By addition of HDAC3 inhibitor, the failed oocyte maturation, over-activation of cell metabolism pathways and H4K16 hyperacetylation are recapitulated, and the overexpression of HDAC3 can rescue the defects of meiotic maturation induced by PSMPs. Our observations suggest a direct link of the maturation defects induced by PSMPs to HDAC3 insufficiency. Thus, we propose the potential treatments for therapy of the failed meiotic maturation of oocyte from women highly exposed to MPs by activating or supplying HDAC3. Overall design: We illustrated the PSMPs exposure induces the over-activation of cell metabolism pathways, insufficient HDACs and H4K16 hyperacetylation in oocytes. In the RNA-seq analysis on oocytes, 5 embryos were used for per reaction and two or three replicates were performed for each group. In the CUT&Tag on oocytes, 20 embryos were used for per reaction and two or three replicates were performed for each group.