Department of Integrative Biology and Pharmacology, The University of Texas Medical School at Houston, Houston, Texas, United States of America.
PLoS One. 2011 Jan 26;6(1):e16456. doi: 10.1371/journal.pone.0016456.
There is a high incidence of infertility in males following traumatic spinal cord injury (SCI). Quality of semen is frequently poor in these patients, but the pathophysiological mechanism(s) causing this are not known. Blood-testis barrier (BTB) integrity following SCI has not previously been examined. The objective of this study was to characterize the effects of spinal contusion injury on the BTB in the rat. 63 adult, male Sprague Dawley rats received SCI (n = 28), laminectomy only (n = 7) or served as uninjured, age-matched controls (n = 28). Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), BTB permeability to the vascular contrast agent gadopentate dimeglumine (Gd) was assessed at either 72 hours-, or 10 months post-SCI. DCE-MRI data revealed that BTB permeability to Gd was greater than controls at both 72 h and 10 mo post-SCI. Histological evaluation of testis tissue showed increased BTB permeability to immunoglobulin G at both 72 hours- and 10 months post-SCI, compared to age-matched sham-operated and uninjured controls. Tight junctional integrity within the seminiferous epithelium was assessed; at 72 hours post-SCI, decreased expression of the tight junction protein occludin was observed. Presence of inflammation in the testes was also examined. High expression of the proinflammatory cytokine interleukin-1 beta was detected in testis tissue. CD68(+) immune cell infiltrate and mast cells were also detected within the seminiferous epithelium of both acute and chronic SCI groups but not in controls. In addition, extensive germ cell apoptosis was observed at 72 h post-SCI. Based on these results, we conclude that SCI is followed by compromised BTB integrity by as early as 72 hours post-injury in rats and is accompanied by a substantial immune response within the testis. Furthermore, our results indicate that the BTB remains compromised and testis immune cell infiltration persists for months after the initial injury.
脊髓损伤(SCI)后男性不育的发生率很高。这些患者的精液质量常常很差,但导致这种情况的病理生理机制尚不清楚。以前没有检查过 SCI 后血睾屏障(BTB)的完整性。本研究的目的是描述大鼠脊髓挫伤损伤对 BTB 的影响。63 只成年雄性 Sprague Dawley 大鼠接受 SCI(n = 28)、椎板切除术(n = 7)或作为未受伤的年龄匹配对照(n = 28)。使用动态对比增强磁共振成像(DCE-MRI),在 SCI 后 72 小时或 10 个月评估血管对比剂钆喷替酸二甲胺(Gd)对 BTB 的通透性。DCE-MRI 数据显示,SCI 后 72 小时和 10 个月时,Gd 对 BTB 的通透性均高于对照组。睾丸组织的组织学评估显示,与年龄匹配的假手术和未受伤对照组相比,SCI 后 72 小时和 10 个月时,免疫球蛋白 G 对 BTB 的通透性增加。评估生精上皮内紧密连接的完整性;在 SCI 后 72 小时,观察到紧密连接蛋白 occludin 的表达减少。还检查了睾丸中的炎症。在睾丸组织中检测到促炎细胞因子白细胞介素-1β的高表达。在急性和慢性 SCI 组的生精上皮中也检测到 CD68(+)免疫细胞浸润和肥大细胞,但在对照组中未检测到。此外,在 SCI 后 72 小时观察到广泛的生殖细胞凋亡。基于这些结果,我们得出结论,早在 SCI 后 72 小时,大鼠的 BTB 完整性就受到损害,并且睾丸内存在大量免疫反应。此外,我们的结果表明,在最初损伤后数月,BTB 仍然受损,睾丸免疫细胞浸润持续存在。