Zearalenone promotes follicle development through activating the SIRT1/PGC-1α signaling pathway in the ovaries of weaned gilts

This study aimed to investigate the effect of zearalenone (ZEA) exposure on follicular development in weaned gilts, and its mechanism based on the silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) signaling pathway. A total of 32 healthy female weaned piglets (Landrace × Yorkshire × Duroc) with an average body weight of 12.39 ± 0.24 kg were randomly allotted to a basal diet supplemented with 0, 0.15, 1.5, or 3.0 mg/kg ZEA for a 32-d feeding test. Blood and ovarian samples were obtained at the end of the experiment to determine serum toxin concentrations, ovarian histology, and the expressions of proliferating cell nuclear antigen (PCNA) and SIRT1/PGC-1α signaling pathway-related genes. Results showed that the vulva area, serum concentrations of ZEA, α-zearalenol and β-zearalenol, the thickness of the growing follicular layer, and the diameter of the largest growing follicles, as well as the expressions of SIRT1, PGC-1α, estrogen-related receptor α (ERRα), ATP synthase subunit beta (ATP5B), and PCNA, increased linearly (P < 0.05) with increasing dietary ZEA, whereas the thickness of the primordial follicle layer decreased linearly (P < 0.05). Immunohistochemical analysis showed that the immunoreactive substances of SIRT1 and PGC-1α in the ovaries enhanced with the increasing dietary ZEA (P < 0.05). In addition, the thickness of the growing follicular layer and the diameter of the largest growing follicle were positively correlated with relative mRNA and protein expressions of SIRT1, PGC-1α, ERRα, ATP5B, and PCNA (P < 0.05). However, the thickness of the primordial follicle layer was negatively correlated with the mRNA and protein expression of SIRT1, PGC-1α, ERRα, ATP5B, and PCNA (P < 0.05). Interestingly, the 1.5 mg/kg ZEA treatment had highly hyperplastic follicles, whereas 3.0 mg/kg ZEA resulted in a large number of follicular atresia, which indicated that low-dose ZEA exposure accelerated follicular proliferation, while high-dose ZEA promoted follicular atresia, although the critical value interval needs further confirmation. Results provide a theoretical basis for finding the therapeutic target of ZEA-induced reproductive disorders in weaned gilts.Zearalenone (ZEA), an estrogenic fusariotoxin, existing in various grains and feedstuffs, could disrupt the endocrine and reproductive systems. However, the underlying mechanisms of ZEA-induced follicular development have not been fully elucidated. This study was to explore the effects and the possible molecular mechanisms of ZEA on follicular development. A total of 32 female weaned piglets were randomly allotted to a basal diet supplemented with 0, 0.15, 1.5, or 3.0 mg/kg ZEA for a 32-d feeding test. The results showed that dietary ZEA increased the vulva area and serum toxin levels, and accelerated follicle development. Moreover, 1.5 and 3.0 mg/kg ZEA changed the expression of proliferating cell nuclear antigen (PCNA) and activated the silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) signaling pathway. Meanwhile, ZEA could promote follicle development by regulating PCNA expression through activation of the SIRT1/PGC-1α signaling pathway. The very significant contribution was that the proliferated follicles significantly increased with the increasing ZEA concentration when the ZEA in the diet was less than 1.5 mg/kg; however, atretic follicles significantly increased when the ZEA in the diet was 3.0 mg/kg. This study provides a theoretical basis for finding the therapeutic target of ZEA-induced reproductive disorders in weaned gilts.