Li Yu, Zhan Mingwei, Li Jindong, Zhang Wei, Shang Xuejun
Department of Urology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China.
Department of Urology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Transl Androl Urol. 2023 Feb 28;12(2):271-285. doi: 10.21037/tau-22-864. Epub 2023 Feb 15.
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.
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.
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.
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.
全身和睾丸感染及炎症会阻碍男性生育能力，这会导致精子发生受损，而抗生素治疗往往无法逆转这种情况。尽管番茄红素（LYC）的作用机制复杂，但有观点认为它可能对保护生育能力有用。本研究探讨了LYC对睾丸损伤的治疗效果及其潜在机制。
腹腔注射脂多糖（LPS；5mg/kg）诱导成熟雄性大鼠睾丸炎症。实验组大鼠经口给予5mg/kg LYC，持续4周。从安乐死的大鼠中取出睾丸进行脂质组学、RNA测序及相关实验检测。
实验室数据表明，LPS诱导的全身炎症会导致睾丸中细胞因子过量和氧化应激。口服LYC可抑制细胞因子过量产生和氧化应激，减轻睾丸损伤。脂质组学研究确定了258种脂质和5条代谢途径有显著变化。结合RNA测序分析，发现1116个基因受到显著调控，并鉴定出许多与脂质代谢相关的信号通路。LYC治疗后，过氧化物酶体增殖物激活受体（PPAR）信号通路中视黄酸X受体α（RXR）的表达显著上调，激活了RXR/PPAR易位二聚体。脂肪酸结合蛋白3（FABP3）和肉碱棕榈酰转移酶1A（CPT1A）等下游基因的表达增加。这些基因参与脂肪酸代谢、脂肪酸降解、脂肪酸链延长和脂质代谢的调控，这部分解释了脂质含量和组成的变化。
LYC调节睾丸脂质代谢及与脂质代谢相关的信号通路，如PPAR信号通路。此外，LYC改善了LPS诱导的睾丸脂质代谢失调以及LPS诱导的炎症反应。本研究为炎症性睾丸损伤机制及潜在治疗靶点的研究提供了新的视角。
