Effect Of Bisphenol F On Meiotic Maturation And Early Embryonic Development Of Mouse Oocytes In Vitro

With socio-economic development,a large number of emerging pollutants,environmental pollution problems are increasingly prominent,which also brings a series of health risks,including plasticizers,personal care products,pesticides and flame retardants,such as environmental endocrine disrupting chemicals(EDCs)have been shown to cause reduced reproductive capacity in female animals.Bisphenol A(BPA),a typical environmental endocrine disruptor,is commonly used in the manufacture of plastic products.A large number of studies have shown that BPA has non-negligible toxicity and endocrine disrupting effects,and thus has been restricted in many countries,resulting in the emergence of "BPA free" products on the market.Bisphenol F(BPF)is one of the largest alternatives to BPA production and use,due to its unique properties,BPF is gradually used in the manufacture of various consumer products.In recent years,BPF has been detected in various environmental media and in plants and animals,indicating its bioaccumulative properties.BPF has been shown to have multiple toxic effects,but studies on its effects on female fertility are still not fully elucidated,and studies on the effects and mechanisms of meiosis and subsequent embryonic development have not been reported.Therefore,in this study,the effects of BPF on meiotic maturation and early embryonic development of mouse oocytes and fertilized eggs were investigated by in vitro culture assays using immunofluorescence and cell live-staining techniques and their mechanisms.This study was divided into two parts,and the results were as follows.1.Effect of BPF on the meiotic maturation of mouse oocytes in vitroIn this study,mouse oocytes were cultured in vitro at the period of germinal vesicle(GV)by adding different concentrations of BPF(0,300,400,500 μM)to the culture medium,and the germinal vesicle breakdown(GVBD)was observed after 2 h.The first polar body extrusion(PBE)was observed after 14 h.Polar body extrusion(PBE)was observed 14 h later.The results showed that the GVBD and PBE rates of 300 μM-treated oocytes decreased significantly.Further study revealed that BPF treatment led to a significant increase in the proportion of abnormal spindle assembly and chromosome arrangement,and the acetylation level of α-microtubulin also increased significantly,indicating that the cytoskeleton was damaged.Meanwhile,BPF treatment led to severe oxidative stress and DNA damage in mouse oocytes,induced early apoptosis,and significantly elevated the expression level of H3K27me3.In addition,this study also compared the effects of BPA and BPF on spindle morphology,oxidative stress and DNA damage in mouse oocytes,and found that BPF caused less damage to spindle morphology than BPA,and both induced the same intensity of oxidative stress,but BPF caused more severe DNA damage in oocytes,suggesting that BPF exerts similar or even greater toxic effects than BPA in some aspects of oocyte maturation process This suggests that BPF exerts similar or even greater toxic effects than BPA in some aspects of oocyte maturation,indicating that BPF is not a safe alternative to BPA.2.Effects of bisphenol F on early embryonic development in miceIn this study,we investigated the effect of BPF on the development of mouse preimplantation embryos.The results showed that compared with oocytes,BPF treatment at lower concentrations(50,75 and 100 μM)inhibited embryonic development,and only a very small number of embryos in the 50 μM treatment group were able to develop to the blastocyst stage,while embryos in the remaining treatment groups were stalled at the4-cell stage,indicating that embryos were less tolerant to BPF toxicity than oocytes.100μM BPF treatment resulted in a highly significant decrease in the 2-cell The treatment with 100 μM BPF caused a significant decrease in 2-cell rate,induced severe DNA damage,and caused a significant decrease in the expression level of H3K27 ac,which may be an important reason for the developmental arrest of early embryos.In summary,this study showed that BPF inhibited meiotic maturation and early embryonic development in mouse oocytes in vitro,as evidenced by a significant decrease in first polar body emission rate and blastocyst rate.BPF can damage oocyte quality by disrupting oocyte cytoskeletal structure,inducing oxidative stress and DNA damage,leading to early apoptosis and altering epigenetic modifications.BPF can damage early oocyte quality by inducing DNA damage and BPF can impair early embryonic quality by inducing DNA damage and altering epigenetic modifications,indicating that BPF is not a safe alternative to BPA.