PMID- 35688042 OWN - NLM STAT- MEDLINE DCOM- 20220621 LR - 20220621 IS - 1879-3231 (Electronic) IS - 0093-691X (Linking) VI - 188 DP - 2022 Aug TI - Dietary supplementation with metformin improves testis function and semen quality and increases antioxidants and autophagy capacity in goats. PG - 79-89 LID - S0093-691X(22)00211-4 [pii] LID - 10.1016/j.theriogenology.2022.05.030 [doi] AB - ATP is essential for mammalian sperm to maintain fertilizing capacity. Metformin (Met) can activate 5'-AMP-activated protein kinase (AMPK) to maintain energy homeostasis. Thus, the aim of the present study was to investigate whether Met can improve testis function, semen quality, antioxidant and autophagy capacity through AMPK mediation of energy metabolism in goats. Twelve adult goats were randomly divided into three dietary treatments. All goats were fed a basal diet for 3 weeks and then assigned to a Met supplementation diet containing 0, 150, or 300 mg/kg for 8 weeks. The results showed that sperm viability, sperm membranal functional integrity, and acrosome integrity increased (P < 0.05) relative to the other treatments in the 300 mg/kg Met group. Growth hormone (GH) and insulin-like growth factor (IGF-1) in the 300 mg/kg Met group significantly decreased (P < 0.05) relative to the control group. Estrogen levels (E(2)) in the 300 mg/kg Met group remarkably improved (P < 0.05) compared with the control group. The activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GSH-px), and superoxide dismutase (SOD) significantly increased (P < 0.05) in the 300 mg/kg Met group relative to the control group. A significant increase in AMPK and p-AMPK protein expression in the 300 mg/kg Met group was observed relative to the control group (P < 0.05). Belicin-1 and LC3II/I protein expression was significantly increased by adding Met to the diet (P < 0.05) and reached a maximum in the 300 mg/kg Met group. In addition, differentially expressed genes (DEGs) of goat testis were confirmed by RNA-seq. GO enrichment analysis revealed that DEGs were enriched in testicular metabolism and sperm development-related functional pathways. Overall, the results indicate that Met may play an important role in the regulation of testis function, semen quality, antioxidant, and autophagy capacity. These findings will help elucidate the role of Met in goat testis development. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Zhao, Jie AU - Zhao J AD - Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, 210095, China. FAU - Yang, Peng-Cheng AU - Yang PC AD - Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, 210095, China. FAU - Yang, Hua AU - Yang H AD - Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, 210095, China. FAU - Wang, Zhi-Bo AU - Wang ZB AD - Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, 210095, China. FAU - El-Samahy, M A AU - El-Samahy MA AD - Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, 210095, China; Animal Production Research Institute, ARC, Ministry of Agriculture, Giza, 12618, Egypt. FAU - Wang, Feng AU - Wang F AD - Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, 210095, China. FAU - Zhang, Yan-Li AU - Zhang YL AD - Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address: zhangyanli@njau.edu.cn. LA - eng PT - Journal Article PT - Randomized Controlled Trial, Veterinary DEP - 20220602 PL - United States TA - Theriogenology JT - Theriogenology JID - 0421510 RN - 0 (Antioxidants) RN - 9100L32L2N (Metformin) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Animals MH - Antioxidants/metabolism MH - Autophagy MH - Dietary Supplements MH - Goats/physiology MH - Male MH - *Metformin/pharmacology MH - *Semen Analysis/veterinary MH - Spermatozoa/physiology MH - Testis/metabolism OTO - NOTNLM OT - Apoptosis OT - Autophagy OT - Go analysis OT - Male reproductive function OT - Metabolism COIS- Declaration of competing interest The authors declare that they have no competing interests. EDAT- 2022/06/11 06:00 MHDA- 2022/06/22 06:00 CRDT- 2022/06/10 18:24 PHST- 2021/11/19 00:00 [received] PHST- 2022/04/10 00:00 [revised] PHST- 2022/05/30 00:00 [accepted] PHST- 2022/06/11 06:00 [pubmed] PHST- 2022/06/22 06:00 [medline] PHST- 2022/06/10 18:24 [entrez] AID - S0093-691X(22)00211-4 [pii] AID - 10.1016/j.theriogenology.2022.05.030 [doi] PST - ppublish SO - Theriogenology. 2022 Aug;188:79-89. doi: 10.1016/j.theriogenology.2022.05.030. Epub 2022 Jun 2.