Olaquindox Negatively Affects Gametes And Reproductive Ability In Mice

Olaquindox,an effective feed additive in livestock industry,has been widely used in animal production.Particularly,OLA has been used in the feed of swine for growth promotion and control swine dysentery or bacterial enteritis in young swine.OLA could potentially expose human into the risk of biological hazards due to its allergic and phototoxicity,genotoxicity and cytotoxicity,mutagenicity,teratogenicity,hepatotoxicity and nephrotoxicity.More importantly,long-term toxicity test results indicate that OLA has moderate to obvious toxicity in animals.Whether the intragastric gavag of OLA has toxic effects on mice fertility and fetal development remain unknown.In this study,we administered ICR mice control saline,low-dose OLA(5 mg/kg/day),and high-dose OLA(60 mg/kg/day)by intragastric gavage for 45 days.We then assessed oocytes morphology and numbers,offspring survival rate,first polar extrusion,ROS level,spindle-chromosome dynamics,mitochondrial distribution,apoptosis,DNA damage and histone modifications for female mice experiments.Similarly,we assessed sperm motility and count,sperm viability,ROS level,mitochondrial membrane potential(MMP)for male mice experiments.Results showed that OLA treatment decreased oocyte numbers and polar body extrusion;rates of in vitro fertilization and embryo development are inhibited.Furthermore,OLA increased ROS level,disrupted MII spindle integrity,caused abnormal mitochondrial distribution,affected H3K4me2 and H3K9me3 levels.Moreover,the oocytes in early apoptosis stages and DNA damage levels have increased in OLA-treated mice along with decreased offspring numbers and survival rates.Similarly,reduced motility,count and viability of sperm were observed in OLA-treated male mice.More importantly,OLA could induce sperm apoptosis and necroses associated with ROS overproduction.In summary,we demonstrated the negative effects of OLA on reproductive abilities in mice.And OLA mediated deterioration of reproduction is associated with ROS overproduction.The mechanism needs to be further explored.