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Impaired macrophages and failure of steroidogenesis and spermatogenesis in rat testes with cytokines deficiency induced by diacerein
Histochemistry and Cell Biology ( IF 2.3 ) Pub Date : 2021-09-13 , DOI: 10.1007/s00418-021-02023-7
Salmo Azambuja de Oliveira 1 , Paulo Sérgio Cerri 2 , Estela Sasso-Cerri 2
Affiliation  

The role of cytokines in testicular function under normal conditions has not been completely understood. Here, we evaluated testicular macrophages (TM), steroidogenesis by Leydig cells (LC) and seminiferous tubules integrity in cytokines-deficient rat testes induced by diacerein, an anti-inflammatory drug that inhibits interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α). Male rats received daily 100 mg/kg of diacerein (DIAG; n = 8) or saline (CG; n = 8) for 30 days. Serum testosterone (T) levels were measured and the seminiferous tubule (ST) area, epithelial area (EA), frequency of damaged ST and number of Sertoli cells (SC) were evaluated. TUNEL method and immunoreactions for detection of pro-IL-1β, TNF-α, steroidogenic acute regulatory protein (StAR), 17β-hydroxysteroid dehydrogenase (17β-HSD), androgen receptor (AR) and scavenger receptor for hemoglobin-haptoglobin complexes (CD163), a TM marker, were performed. Testicular AR, 17β-HSD and IL-1β levels were detected by Western blot. Data were submitted to Student t test (p ≤ 0.05). In DIAG, T and testicular AR, 17β-HSD and IL-1β levels decreased significantly (p < 0.05). The number of TUNEL-positive interstitial cells increased and LC showed weak StAR, 17β-HSD and AR immunoexpression in association with reduced IL-1β immunoexpression and number of CD163-positive TM in the interstitial tissue from diacerein-treated rats. Numerous damaged ST were found in DIAG, and reduction in the EA were associated with germ cells death. Moreover, the number of SC reduced and weak AR and TNF-α immunoexpression was observed in SC and germ cells, respectively. The cytokines deficiency induced by diacerein impairs TM, LC and spermatogenesis, and points to a role of IL-1β in steroidogenesis under normal conditions. In the ST, the weak AR and TNF-α immunoexpression in SC and germ cells, respectively, reinforces the idea that TNF-α plays a role in the SC androgenic control.



中文翻译:

双醋瑞因诱导的细胞因子缺乏大鼠睾丸中巨噬细胞受损和类固醇生成和精子生成失败

在正常条件下,细胞因子在睾丸功能中的作用尚未完全清楚。在这里,我们评估了双醋瑞因(一种抑制白介素-1(IL-1)和肿瘤坏死因子的抗炎药)诱导的细胞因子缺乏大鼠睾丸中睾丸巨噬细胞(TM)、睾丸间质细胞(LC)的类固醇生成和曲细精管的完整性。 -α (TNF-α)。雄性大鼠每天接受 100 mg/kg 双醋瑞因 (DIAG; n  = 8) 或生理盐水 (CG; n = 8) 30 天。测量血清睾酮 (T) 水平并评估曲细精管 (ST) 面积、上皮面积 (EA)、受损 ST 的频率和支持细胞 (SC) 的数量。用于检测 pro-IL-1β、TNF-α、类固醇生成急性调节蛋白 (StAR)、17β-羟基类固醇脱氢酶 (17β-HSD)、雄激素受体 (AR) 和血红蛋白-触珠蛋白复合物清除受体 (CD163) 的 TUNEL 方法和免疫反应),一个 TM 标记,进行了。Western blot检测睾丸AR、17β-HSD和IL-1β水平。数据提交学生t检验p≤0.05  )。在 DIAG、T 和睾丸 AR 中,17β-HSD 和 IL-1β 水平显着下降(p < 0.05)。TUNEL 阳性间质细胞数量增加,LC 显示弱 StAR、17β-HSD 和 AR 免疫表达,这与双醋瑞因处理大鼠间质组织中 IL-1β 免疫表达和 CD163 阳性 TM 数量减少有关。在 DIAG 中发现了许多受损的 ST,并且 EA 的减少与生殖细胞死亡有关。此外,分别在 SC 和生殖细胞中观察到 SC 减少和弱 AR 和 TNF-α 免疫表达的数量。双醋瑞因诱导的细胞因子缺乏会损害 TM、LC 和精子发生,并指出 IL-1β 在正常条件下在类固醇生成中的作用。在 ST 中,SC 和生殖细胞中的弱 AR 和 TNF-α 免疫表达分别强化了 TNF-α 在 SC 雄激素控制中起作用的观点。

更新日期:2021-09-13
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