PMID- 37934018 OWN - NLM STAT- MEDLINE DCOM- 20231128 LR - 20231128 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 37 IP - 12 DP - 2023 Dec TI - UCHL1 maintains microenvironmental homeostasis in goat germline stem cells. PG - e23306 LID - 10.1096/fj.202301674RR [doi] AB - Spermatogonial stem cells (SSCs) play a crucial role in mammalian spermatogenesis and maintain the stable inheritance of the germline in livestock. However, stress and bacterial or viral infections can disrupt immune homeostasis of the testes, thereby leading to spermatogenesis destruction and infertility, which severely affects the health and productivity of mammals. This study aimed to explore the effect of ubiquitin C-terminal hydrolase L1 (UCHL1) knockdown (KD) in goat SSCs and mouse testes and investigate the potential anti-inflammatory function of UCHL1 in a poly(I:C)-induced inflammation model to maintain microenvironmental homeostasis. In vitro, the downregulation of UCHL1 (UCHL1 KD) in goat SSCs increased the expression levels of apoptosis and inflammatory factors and inhibited the self-renewal and proliferation of SSCs. In vivo, the structure of seminiferous tubules and spermatogenic cells was disrupted after UCHL1 KD, and the expression levels of apoptosis- and inflammation-related proteins were significantly upregulated. Furthermore, UCHL1 inhibited the TLR3/TBK1/IRF3 pathway to resist poly(I:C)-induced inflammation in SSCs by antagonizing HSPA8 and thus maintaining SSC autoimmune homeostasis. Most importantly, the results of this study showed that UCHL1 maintained immune homeostasis of SSCs and spermatogenesis. UCHL1 KD not only inhibited the self-renewal and proliferation of goat SSCs and spermatogenesis but was also involved in the inflammatory response of goat SSCs. Additionally, UCHL1 has an antiviral function in SSCs by antagonizing HSPA8, which provides an important basis for exploring the specific mechanisms of UCHL1 in goat spermatogenesis. CI - (c) 2023 Federation of American Societies for Experimental Biology. FAU - Yang, Donghui AU - Yang D AUID- ORCID: 0000-0002-1516-9875 AD - College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China. FAU - Zhang, Mengfei AU - Zhang M AUID- ORCID: 0000-0002-4606-8444 AD - College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China. FAU - Chen, Wenbo AU - Chen W AUID- ORCID: 0000-0001-7195-8564 AD - College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China. FAU - Lu, Qizhong AU - Lu Q AUID- ORCID: 0000-0001-6992-1500 AD - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Wan, Shicheng AU - Wan S AUID- ORCID: 0009-0009-6446-2339 AD - College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China. FAU - Du, Xiaomin AU - Du X AUID- ORCID: 0000-0002-9300-1971 AD - College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China. AD - Shaanxi Provincial Engineering and Technology Research Center of Cashmere Goats, College of Life Sciences, Yulin University, Yulin, China. FAU - Li, Yunxiang AU - Li Y AUID- ORCID: 0000-0002-3126-6050 AD - College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China. FAU - Li, Balun AU - Li B AUID- ORCID: 0000-0001-9835-0436 AD - College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China. FAU - Wu, Wenping AU - Wu W AUID- ORCID: 0009-0005-7648-750X AD - College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China. FAU - Wang, Congliang AU - Wang C AUID- ORCID: 0009-0005-2232-2101 AD - College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China. FAU - Li, Na AU - Li N AUID- ORCID: 0000-0002-4112-0944 AD - College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China. FAU - Peng, Sha AU - Peng S AUID- ORCID: 0000-0001-6678-5582 AD - College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China. FAU - Tang, Haiyang AU - Tang H AUID- ORCID: 0000-0001-9537-2891 AD - State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. FAU - Hua, Jinlian AU - Hua J AUID- ORCID: 0000-0001-9788-8592 AD - College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 SB - IM MH - Animals MH - Male MH - Mice MH - *Goats MH - Homeostasis MH - Inflammation/metabolism MH - Spermatogenesis/physiology MH - *Spermatogonia/metabolism MH - Stem Cells MH - Testis/metabolism OTO - NOTNLM OT - SSCs OT - UCHL1 OT - goat OT - homeostasis OT - spermatogenesis EDAT- 2023/11/07 12:44 MHDA- 2023/11/08 06:43 CRDT- 2023/11/07 09:23 PHST- 2023/10/26 00:00 [revised] PHST- 2023/08/17 00:00 [received] PHST- 2023/10/30 00:00 [accepted] PHST- 2023/11/08 06:43 [medline] PHST- 2023/11/07 12:44 [pubmed] PHST- 2023/11/07 09:23 [entrez] AID - 10.1096/fj.202301674RR [doi] PST - ppublish SO - FASEB J. 2023 Dec;37(12):e23306. doi: 10.1096/fj.202301674RR.