Zearalenone-Promoted Follicle Growth through Modulation of Wnt-1/β-Catenin Signaling Pathway and Expression of Estrogen Receptor Genes in Ovaries of Postweaning Piglets

Feedstuffs are severely contaminated by zearalenone (ZEA) worldwide. A specific dietary level of ZEA could cause malformations of the reproductive organs of sows, false estrus, decreased litter size, and abortion. However, the underlying mechanisms are still not clear. The objectives of the present study were to assess the effects of ZEA on morphology, distribution, and expression of estrogen receptors (ER alpha and ER beta) in the ovaries of postweaning piglets. Furthermore, the relationship between ERs/glycogen synthase kinase (GSK)-3 beta-dependent pathways mediated by ZEA and the Wnt-1/beta-catenin signaling pathway was examined. Forty healthy weaning piglets were allocated to the following four treatment groups: piglets fed with basal diet only (control), and ZEA0.5, ZEA1.0, and ZEA1.5, which were fed basal diets supplemented with ZEA at 0.5, 1.0, and 1.5 mg.kg(-1), respectively. Then, the expression of GSK-3 beta, ER alpha, ER beta and Wnt-1/beta-catenin were examined histomorphologically and immunohistochemically. Results showed that the proportion of primordial follicles (PrF's) decreased (p < 0.001) but that of atretic primordial follicles (APFs) increased (p < 0.001) with increasing dietary ZEA levels. More interestingly, the immunopositivity of ER beta in the ovaries was stronger than that of ER alpha with the same treatment. The relative mRNA and protein expression levels of ER alpha, ER beta, Wnt-1, beta-catenin, and GSK-3 beta in the ovaries of postweaning gilts increased linearly (p < 0.05) as dietary ZEA concentrations increased. Moreover, the accumulation of Wnt-1 and beta-catenin in the ovaries indicated that ZEA activated the Wnt-1/beta-catenin pathway, mediated by ERs/GSK-3 beta. Our results strongly suggested that ovarian follicles in the ZEA (0.5-1.5 mg.kg(-1))-treated groups were highly proliferative state, indicating that ZEA promoted ovarian development. The results also suggested that ZEA activates the ERs/GSK-3 beta-dependent Wnt-1/beta-catenin signaling pathway, indicating its important role in accelerating development of the ovaries.