Ma Junyuan, Yang Yanmei, He Lin, Yang Chongfa, Yang Yahua, Li Yang, He Wen, Niu Xiaoying, Chen Zhou, Hu Songming, Wang Jin'e, Zhaxi Yingpai, Huo Shengdong
College of Life Science and Engineering, Northwest Minzu University, Lanzhou, Gansu, 730030, China; Gannan Livestock Technical Service Center, Gannan, Gansu, 747000, China.
College of Life Science and Engineering, Northwest Minzu University, Lanzhou, Gansu, 730030, China.
Domest Anim Endocrinol. 2025 Apr;91:106906. doi: 10.1016/j.domaniend.2024.106906. Epub 2024 Dec 10.
Estradiol (E2) secreted by Leydig cells (LCs) can accumulate in the testes due to constriction of the reproductive lumen. Estrogen is not only important for reproduction, but also protects against inflammation. In this study, the role of pyroptosis in testicular inflammation and the effects of E2 against inflammation and pyroptosis of yak interstitial cells were investigated. Inflamed testes exhibited structural damage and pyroptosis with decreased E2, testosterone, and estrogen receptor β (ERβ) levels in testicular fluid. E2 alone inhibited testosterone secretion and increased ERβ expression in mature LCs. In LCs, lipopolysaccharide (LPS) causes inflammation by activation of TNF-α and IL-6, and pyroptosis via activation of the classical and non-classical pyroptosis pathways. LPS inhibits sex hormone secretion and ERβ expression in LCs. E2 inhibited the LPS-induced decrease of ER expression in LCs and also inhibited LPS-induced interstitial cell inflammation and pyroptosis, which was partially blocked by Selisistat (EX-527, SIRT1 inhibitor) or Fulvestrant (ICI 182,780, E2 non-genomic receptor inhibitors). In conclusion, E2 relieved LPS-induced inflammation and pyroptosis of yak LCs via the SIRT1/Nox4/ROS pathway. This finding provides new insights into the role of estrogen in male reproductive health and offers a potential therapeutic strategy to improve testicular immune and reproductive function by modulating hormonal homeostasis.
睾丸间质细胞（LCs）分泌的雌二醇（E2）可因生殖管腔狭窄而在睾丸中蓄积。雌激素不仅对生殖很重要，还具有抗炎作用。在本研究中，探讨了细胞焦亡在睾丸炎症中的作用以及E2对牦牛间质细胞炎症和细胞焦亡的影响。发炎的睾丸表现出结构损伤和细胞焦亡，睾丸液中E2、睾酮和雌激素受体β（ERβ）水平降低。单独使用E2可抑制睾酮分泌并增加成熟LCs中ERβ的表达。在LCs中，脂多糖（LPS）通过激活TNF-α和IL-6引起炎症，并通过激活经典和非经典细胞焦亡途径导致细胞焦亡。LPS抑制LCs中性激素分泌和ERβ表达。E2抑制LPS诱导的LCs中ER表达的降低，还抑制LPS诱导的间质细胞炎症和细胞焦亡，而这一作用被Selisistat（EX-527，SIRT1抑制剂）或氟维司群（ICI 182,780，E2非基因组受体抑制剂）部分阻断。总之，E2通过SIRT1/Nox4/ROS途径减轻LPS诱导的牦牛LCs炎症和细胞焦亡。这一发现为雌激素在男性生殖健康中的作用提供了新的见解，并为通过调节激素稳态改善睾丸免疫和生殖功能提供了潜在的治疗策略。
