MEHP-induced rat testicular inflammation does not exacerbate germ cell apoptosis.
MEHP-induced rat testicular inflammation does not exacerbate germ cell apoptosis.
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MEHP诱导的大鼠睾丸炎症不会加剧生殖细胞凋亡。
DOI：
10.1530/rep-18-0093
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Richburg JH
中科院分区：
文献类型：
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作者：
Voss JJLP;Stermer AR;Ghaffari R;Tiwary R;Richburg JH
睾丸是维持免疫抑制环境的器官。我们之前发现，青春期前的大鼠暴露于急性剂量的支持细胞毒剂邻苯二甲酸单（2-乙基己基）酯（MEHP）中，会导致睾丸间质中 CD11b+ 免疫细胞的积累，这与生殖细胞（GC）凋亡的强烈发生率密切相关。在这里，我们检验了浸润性免疫细胞导致 GC 凋亡的假设。出生后第 28 天接受口服剂量 700 mg/kg MEHP 的 Fischer 大鼠显示 CD11bc+/CD68+/CD163- 巨噬细胞和中性粒细胞显着浸润。渗透在 12 小时达到峰值，但在 48 小时有所减少。 MEHP 治疗大鼠的睾丸巨噬细胞显示 Tnfa 和 Il6 表达显着上调，并且与对照组相比，Arg1/Nos2 比率降低。然而，还观察到抗炎基因 Il10 和 Tgfb1 的小幅增加。在 MEHP 治疗之前用氯膦酸盐脂质体消耗循环单核细胞减少了巨噬细胞流入睾丸，但并没有降低 GC 细胞凋亡。此外，使用抗多形核细胞抗体去除中性粒细胞可阻止巨噬细胞和中性粒细胞浸润睾丸，但也不影响 GC 凋亡。总之，这些结果表明，暴露于 MEHP 会导致促炎单核细胞和中性粒细胞快速暂时流入睾丸间质。然而，在这种急性给药模式下，这些浸润性白细胞似乎不会促进 MEHP 诱导的睾丸 GC 凋亡，从而导致这些浸润细胞在 MEHP 诱导的睾丸损伤发病机制中的功能意义尚未解决。
The testis is an organ that maintains an immune suppressive environment. We previously revealed that exposure of pre-pubertal rats to an acute dose of a well-described Sertoli cell toxicant, mono-(2-ethylhexyl) phthalate (MEHP), leads to an accumulation of CD11b+ immune cells in the testicular interstitial space that closely correlates with a robust incidence of germ cell (GC) apoptosis. Here we test the hypothesis that the infiltrating immune cells contribute to GC apoptosis. Postnatal day 28 Fischer rats that received an oral dose of 700 mg/kg MEHP showed a significant infiltration of both CD11bc+/CD68+/CD163- macrophages and neutrophils. The infiltration peaked at 12 hours, but had reduced by 48 hours. Testicular macrophages from MEHP-treated rats showed significantly upregulated expression of Tnfa and Il6, and the Arg1/Nos2 ratio was reduced compared to controls. However, small increases in anti-inflammatory genes Il10 and Tgfb1 were also observed. Depletion of circulating monocytes with clodronate liposomes prior to MEHP-treatment reduced the macrophage influx into the testis, but did not lower GC apoptosis. Additionally, depletion of neutrophils using an anti-polymorphonuclear cell antibody prevented both macrophage and neutrophil infiltration into the testis, but also did not affect GC apoptosis. Together, these results show that exposure to MEHP leads to a rapid and temporary influx of pro-inflammatory monocytes and neutrophils in the interstitium of the testis. However, with this acute dosing paradigm, these infiltrating leukocytes do not appear to contribute to MEHP-induced testicular GC apoptosis leaving the functional significance of these infiltrating cells in the pathogenesis of MEHP-induced testicular injury unresolved.