Exposure To Acrylonitrile Affected Ovarian Function,Oocyte Quality And Offspring Development In Mice

The female reproductive system has important physiological functions of mammalian reproduction,including meiosis of oocytes,development and regulation of ovarian follicles,synthesis and secretion of hypothalamic pituitary gonadal axis hormones and so on.With the wide application of industrial products,the environment is full of chemicals with unknown toxicity,and environmental factors significantly affect female reproductive function.When environmental pollution exposure causes female reproductive toxicity,it will inevitably lead to fertility decline,female premature ovarian failure,male sperm motility decline and genetic defects of newborn fetus.Acrylonitrile belongs to organic cyanide and is widely used in industry to produce rubber,resin,plastic and synthetic fiber.However,while acrylonitrile is widely used,the biological toxicity caused by its environmental residues has attracted widespread attention.It has been proved that acrylonitrile can have toxic effects on the immune system,respiratory system,nervous system and digestive system,but its reproductive toxicity to female mammals is not clear.Therefore,the study and analysis of the reproductive toxicity of acrylonitrile is helpful to improve the understanding of its biological toxicity.In this study,acrylonitrile was used to establish a mouse intragastric toxicological model to study and analyze its toxic effect on mammalian female reproductive function.We first found that acrylonitrile treatment reduced the body weight and ovarian coefficient of mice,and caused abnormal estrous cycle.In the stable ovarian environment,acrylonitrile leads to impaired follicular development and shows high levels of inflammation and apoptosis in follicles.At the same time,during oocyte development,acrylonitrile leads to the reduction of oocytes in the germinal vesicle stage and the middle stage of the second meiosis.Transcriptomic analysis of oocytes showed that acrylonitrile changed the expression of oocyte genes related to apoptosis,oxidative stress,endoplasmic reticulum stress and autophagy.Further molecular biology experiments showed that acrylonitrile induced early apoptosis,DNA damage,elevated levels of reactive oxygen species,abnormal endoplasmic reticulum and lysosomal aggregation.We also observed the abnormal distribution of mitochondria,the destruction of ultrastructure and the depolarization of mitochondrial membrane potential.For the effect of offspring,we found that acrylonitrile treatment reduced the number and weight of newborn fetuses in mice.In conclusion,the results of this study show that acrylonitrile will damage the stability of the internal environment of the ovary,thus affecting the development of oocytes and reducing the number of offspring,which has female reproductive toxicity to mammals.