PMID- 36915878
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230315
IS  - 2223-4691 (Print)
IS  - 2223-4691 (Electronic)
IS  - 2223-4683 (Linking)
VI  - 12
IP  - 2
DP  - 2023 Feb 28
TI  - Lycopene alleviates lipopolysaccharide-induced testicular injury in rats by 
      activating the PPAR signaling pathway to integrate lipid metabolism and the 
      inflammatory response.
PG  - 271-285
LID - 10.21037/tau-22-864 [doi]
AB  - BACKGROUND: Male fertility can be hampered by systemic and testicular infections 
      and inflammation, which can lead to impaired spermatogenesis that often cannot be 
      reversed by antibiotic treatment. There has been some suggestion that lycopene 
      (LYC) may be useful in the preservation of fertility, although its mechanisms are 
      complex. This current study examined the therapeutic efficacy of LYC on 
      testicular damage and its underlying mechanisms. METHODS: Lipopolysaccharide 
      (LPS; 5 mg/kg) was injected intraperitoneally to induce inflammation of the 
      testes in mature male rats. The rats in the experimental group were administered 
      5 mg/kg LYC intragastrically for 4 weeks. The testes were harvested from the 
      euthanized rats for lipidomics, RNA sequencing, and related experimental tests. 
      RESULTS: Laboratory data suggested that LPS-induced systemic inflammation induced 
      cytokine excess and oxidative stress in the testes. Administration of oral LYC 
      inhibited the excess cytokine production and oxidative stress, mitigating damage 
      to the testes. Lipidomic studies identified significant changes to 258 lipids and 
      5 metabolism pathways. Coupled with RNA sequencing analysis, 1,116 genes were 
      found to be significantly regulated and many lipid metabolism-related signaling 
      pathways were identified. The expression of retinoid X receptor alpha (RXR) in 
      the peroxisome proliferator-activated receptor (PPAR) signaling pathway was 
      significantly upregulated after LYC treatment, which activated the RXR/PPAR easy 
      dimer. The expression of downstream genes such as fatty acid binding protein 3 
      (FABP3) and carnitine palmitoyltransferase 1A (CPT1A) was increased. These genes 
      are involved in the control of fatty acid metabolism, fatty acid degradation, 
      fatty acid chain elongation, and lipid metabolism, which partially explains the 
      changes in the content and composition of lipids. CONCLUSIONS: LYC regulates the 
      lipid metabolism of testes and lipid metabolism-related signaling pathways, such 
      as the PPAR signaling pathway. Furthermore, LYC ameliorated the LPS-induced 
      dysregulation of lipid metabolism in the testes, as well as the LPS-induced 
      inflammatory response. This study offers a new perspective for the investigation 
      of the mechanisms in inflammatory testicular damage and potential therapeutic 
      targets.
CI  - 2023 Translational Andrology and Urology. All rights reserved.
FAU - Li, Yu
AU  - Li Y
AD  - Department of Urology, Jinling Hospital, The First School of Clinical Medicine, 
      Southern Medical University, Nanjing, China.
FAU - Zhan, Mingwei
AU  - Zhan M
AD  - Department of Urology, Jinling Hospital, School of Medicine, Nanjing University, 
      Nanjing, China.
FAU - Li, Jindong
AU  - Li J
AD  - Department of Urology, Jinling Hospital, The First School of Clinical Medicine, 
      Southern Medical University, Nanjing, China.
AD  - Central South University Xiangya School of Medicine Affiliated Haikou Hospital, 
      Haikou, China.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Urology, Jinling Hospital, School of Medicine, Nanjing University, 
      Nanjing, China.
FAU - Shang, Xuejun
AU  - Shang X
AD  - Department of Urology, Jinling Hospital, The First School of Clinical Medicine, 
      Southern Medical University, Nanjing, China.
AD  - Department of Urology, Jinling Hospital, School of Medicine, Nanjing University, 
      Nanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20230215
PL  - China
TA  - Transl Androl Urol
JT  - Translational andrology and urology
JID - 101581119
PMC - PMC10006007
OTO - NOTNLM
OT  - Transcriptome
OT  - inflammatory infertility
OT  - lipidomics
OT  - oxidative stress
OT  - testis
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://tau.amegroups.com/article/view/10.21037/tau-22-864/coif). The authors 
      have no conflicts of interest to declare.
EDAT- 2023/03/15 06:00
MHDA- 2023/03/15 06:01
PMCR- 2023/02/28
CRDT- 2023/03/14 02:14
PHST- 2022/12/01 00:00 [received]
PHST- 2023/02/06 00:00 [accepted]
PHST- 2023/03/14 02:14 [entrez]
PHST- 2023/03/15 06:00 [pubmed]
PHST- 2023/03/15 06:01 [medline]
PHST- 2023/02/28 00:00 [pmc-release]
AID - tau-12-02-271 [pii]
AID - 10.21037/tau-22-864 [doi]
PST - ppublish
SO  - Transl Androl Urol. 2023 Feb 28;12(2):271-285. doi: 10.21037/tau-22-864. Epub 
      2023 Feb 15.