PMID- 35213700 OWN - NLM STAT- MEDLINE DCOM- 20220412 LR - 20230226 IS - 1525-3163 (Electronic) IS - 0021-8812 (Print) IS - 0021-8812 (Linking) VI - 100 IP - 4 DP - 2022 Apr 1 TI - Zearalenone promotes follicle development through activating the SIRT1/PGC-1alpha signaling pathway in the ovaries of weaned gilts. LID - 10.1093/jas/skac058 [doi] LID - skac058 AB - 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-gamma co-activator 1alpha (PGC-1alpha) signaling pathway. A total of 32 healthy female weaned piglets (Landrace x Yorkshire x 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-1alpha signaling pathway-related genes. Results showed that the vulva area, serum concentrations of ZEA, alpha-zearalenol and beta-zearalenol, the thickness of the growing follicular layer, and the diameter of the largest growing follicles, as well as the expressions of SIRT1, PGC-1alpha, estrogen-related receptor alpha (ERRalpha), 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-1alpha 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-1alpha, ERRalpha, 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-1alpha, ERRalpha, 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. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. 
For permissions, please e-mail: journals.permissions@oup.com. FAU - Wan, Boyang AU - Wan B AD - Department of Animal Sciences and Technology and Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong 271018, China. FAU - Huang, Libo AU - Huang L AUID- ORCID: 0000-0002-2318-1954 AD - Department of Animal Sciences and Technology and Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong 271018, China. FAU - Jing, Changwei AU - Jing C AD - Technical Department, Shandong Chinwhiz Co., Weifang, Shandong 262400, China. FAU - Li, Yang AU - Li Y AD - Department of Animal Sciences and Technology and Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong 271018, China. FAU - Jiao, Ning AU - Jiao N AD - Department of Animal Sciences and Technology and Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong 271018, China. FAU - Liang, Ming AU - Liang M AD - Department of Feeding Microecology, Shandong Baolaililai Bioengineering Co., Ltd., Taian, Shandong 271001, China. FAU - Jiang, Shuzhen AU - Jiang S AD - Department of Animal Sciences and Technology and Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong 271018, China. FAU - Yang, Weiren AU - Yang W AD - Department of Animal Sciences and Technology and Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong 271018, China. LA - eng GR - ZR2021MC048/Natural Science Foundation of Shandong Province/ GR - SDAIT-08-04/Shandong Province Pig Industry Technology System/ GR - 2019JZZY020609/Major Innovative Projects of Shandong Province/ PT - Journal Article PL - United States TA - J Anim Sci JT - Journal of animal science JID - 8003002 RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - 0 (Proliferating Cell Nuclear Antigen) RN - 0 (RNA, Messenger) RN - 5W827M159J (Zearalenone) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - Animals MH - Female MH - Follicular Atresia MH - Ovary/metabolism MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics MH - Proliferating Cell Nuclear Antigen/metabolism MH - RNA, Messenger/metabolism MH - Signal Transduction MH - Sirtuin 1/genetics/metabolism/pharmacology MH - Sus scrofa/genetics MH - Swine MH - *Zearalenone/pharmacology PMC - PMC9030242 OAB - 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-gamma co-activator 1alpha (PGC-1alpha) signaling pathway. Meanwhile, ZEA could promote follicle development by regulating PCNA expression through activation of the SIRT1/PGC-1alpha 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. OABL- eng OTO - NOTNLM OT - SIRT1/PGC-1alpha pathway OT - follicle development OT - gilt OT - ovary OT - zearalenone EDAT- 2022/02/26 06:00 MHDA- 2022/04/13 06:00 PMCR- 2023/02/25 CRDT- 2022/02/25 17:16 PHST- 2022/01/07 00:00 [received] PHST- 2022/02/24 00:00 [accepted] PHST- 2022/02/26 06:00 [pubmed] PHST- 2022/04/13 06:00 [medline] PHST- 2022/02/25 17:16 [entrez] PHST- 2023/02/25 00:00 [pmc-release] AID - 6537148 [pii] AID - skac058 [pii] AID - 10.1093/jas/skac058 [doi] PST - ppublish SO - J Anim Sci. 2022 Apr 1;100(4):skac058. doi: 10.1093/jas/skac058.