Microplastics(MPs)are considered one of the main causes of male and female infertility.However,the reproductive toxicity and its related mechanisms are currently understood primarily through animal models with acute e...Microplastics(MPs)are considered one of the main causes of male and female infertility.However,the reproductive toxicity and its related mechanisms are currently understood primarily through animal models with acute exposure to MPs.In this study,we demonstrate that lowdose exposure to polystyrene microplastics(PSMPs)leads to severely abnormal reproduction in females,manifested by oocyte meiotic maturation defect.Mechanistically,PSMPs exposure induce the overactivation of cell metabolism pathways,insufficient HDACs,and H4K16 hyperacetylation in oocytes both in vivo and in vitro.When an HDAC3 inhibitor is added,the oocyte maturation defect,overactivation of cell metabolism pathways,and H4K16 hyperacetylation are recapitulated.Conversely,the overexpression of HDAC3 can rescue the defects in meiotic maturation induced by PSMPs.Our observations suggest a direct link between the maturation defects caused by PSMPs and HDAC3 insufficiency.Thus,we propose potential treatments to address the meiotic maturation defect of oocytes in women highly exposed to MPs by activating or supplying HDAC3.展开更多
基金supported by the National Natural Science Foundation of China(32370862)Basic Public Welfare Research Program of Zhejiang Province(LY22C120001)Natural Science Foundation of Zhejiang Province(LQ24C120002).
文摘Microplastics(MPs)are considered one of the main causes of male and female infertility.However,the reproductive toxicity and its related mechanisms are currently understood primarily through animal models with acute exposure to MPs.In this study,we demonstrate that lowdose exposure to polystyrene microplastics(PSMPs)leads to severely abnormal reproduction in females,manifested by oocyte meiotic maturation defect.Mechanistically,PSMPs exposure induce the overactivation of cell metabolism pathways,insufficient HDACs,and H4K16 hyperacetylation in oocytes both in vivo and in vitro.When an HDAC3 inhibitor is added,the oocyte maturation defect,overactivation of cell metabolism pathways,and H4K16 hyperacetylation are recapitulated.Conversely,the overexpression of HDAC3 can rescue the defects in meiotic maturation induced by PSMPs.Our observations suggest a direct link between the maturation defects caused by PSMPs and HDAC3 insufficiency.Thus,we propose potential treatments to address the meiotic maturation defect of oocytes in women highly exposed to MPs by activating or supplying HDAC3.
