Effects Of Zearalenone On Immunotoxicity And Reproductive Toxicity Of Post-weaning Piglets

As one of the highest levels of mycotoxin detected in Chinese feed materials and mixed feed,Zearalenone(ZEA)has a similar structure with estrogen.ZEA can disrupt hormone metabolism by participating in the activation of estrogen responsive genes,causing reproductive dysfunction.The existence of ZEA in the diet is an important factor leading to precocious puberty and reproductive disorders.In recent years,the pollution of ZEA is becoming more universal,and the decline in fecundity and immunosuppression of the sows caused by the intake of ZEA contaminated feed seriously hindered the development of the pig industry.In order to explore the effects of different levels of ZEA contaminated diet on immune toxicity and reproductive toxicity of post-weaning piglets,and further grope for the mechanism of Wnt/β-catenin in ZEA induced post-weaning piglets’ ovary development.Forty healthy post-weaning piglets(Duroc × Landrace × Large white)were allocated into 4 groups according to age(35 ± 1 days of age)and average body weight(14.01 ± 0.86 kg).Animals were fed individually in a metabolic cage for 35 days after 10-d adaptation.Piglets in control were fed with basal diet only(Control),and test 1,2 and 3 were basal diet supplemented with ZEA at the level of 0,0.5,1.0 or 1.5 mg/kg,with analyzed ZEA concentrations of 0,0.52 ±0.07,1.04 ± 0.03 and 1.51 ± 0.13 mg/kg,respectively.Results indicated that the average daily feed intake,average daily gain and feed weight ratio(F/G)had no significant effect by the ZEA level in diet of post-weaning piglets(P >0.05),however,with the level of ZEA increasing,the F/G showed a linear decline(P = 0.075);Compared with the control,activity of glutathione peroxidase(GSH-Px)in 0.5,1.0 and 1.5mg/kg ZEA treatments,antibody level of the classical swine fever and pseudorabies gPI in 1.0and 1.5 mg/kg ZEA treatments,porcinereproductive and respiratory syndrome antibody level in 1.5 mg/kg ZEA treatment,and lymphocyte proliferation rate in 1.0 and 1.5 mg/kg ZEAtreatment were significantly decreased(P < 0.05).However,concentration of malondialdehyde(MDA)in 0.5,1.0 and 1.5 mg/kg ZEA treatments increased significantly(P< 0.05);The ovary organ index showed a linear increase(P < 0.01)with the increasing ZEA level in the diet of post-weaning piglets.The ovary organ index in 1.0 mg/kg treatment was significantly higher than that of 1.5 mg/kg treatment(P < 0.05),and the ovary organ index in1.5 mg/kg treatment was significantly higher than that of 0.5 mg/kg and control treatments(P < 0.05);The relative mRNA expression of estrogen receptor α(ERα),estrogen receptor β(ERβ),progesterone receptor(PR),Wnt-1,β-catenin and glycogen synthase kinase 3β(GSK-3β)showed a linear increase(P < 0.01),and the relative protein expression of ERα,ERβ,PR,Wnt-1,β-catenin and GSK-3β also showed a linear increase(P < 0.01)with the increasing ZEA level in the diet of post-weaning piglets.The results of immunohistochemistry showed that the immunoreactive substance of ERα,ERβ and PR in ovaries were mainly distributed in oocytes and granulosa cells,theca cells and vascular wall cells of primordial follicles and growing follicles.The proportion of primordial follicles(PrF)decreased significantly with the increasing ZEA levels(P < 0.001),however,the atresia of primordial follicles(APF)proportion increased significantly with the increasing ZEA levels(P < 0.001),and the number of PrF in the 1.0 mg/kg group reached the highest,and a large number of APF appeared in the 1.5 mg/kg group.With the increase of ZEA level and the degree of follicular atresia,immunoreactivity was significantly enhanced.There was no significant change in the distribution of immunoreactive substance of ERα,ERβ and PR in the ovary,due to the presence of ZEA.Taken together,(1)ZEA at 0.5 mg/kg was sufficient to induce oxidative stress in post-weaning piglets,and the content of ZEA in the diet was dose-dependent;(2)ZEA at 1.0mg/kg was sufficient to induce Immuno toxicity and cytotoxicity in post-weaning piglets;(3)ZEA(0.5~1.5 mg/kg)changed the development of follicle and ovary,eventually,induced reproductive toxicity through the activation of PR,ERs/GSK-3β-dependent Wnt/β-catenin signaling pathway.