Disturbed spermatogenesis associated with thickened lamina propria of seminiferous tubules is not caused by dedifferentiation of myofibroblasts
Disturbed spermatogenesis associated with thickened lamina propria of seminiferous tubules is not caused by dedifferentiation of myofibroblasts
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DOI：
10.1093/humrep/der077
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发表时间：
2011-06-01
影响因子：
6.1
通讯作者：
Middendorff, R.
中科院分区：
文献类型：
--
作者：
Volkmann, J.;Mueller, D.;Middendorff, R.
背景：在人类睾丸中，肌成纤维细胞是曲细精管固有层的主要细胞成分。在大量不孕症患者中发现增厚的(纤维化的)LP和扩张的小管，而肌纤维母细胞去分化已在老年男性中被描述。然而，目前尚不清楚肌成纤维细胞的去分化是否与LP改变相关的生精障碍有关。方法：采用新的组织学和形态计量学方法、激光显微解剖后的RT-PCR和Western blotting对35例不育男性睾丸组织的LP进行研究。结果：所有生精小管的LP中均有肌成纤维细胞。根据LP的形态，可将每一小管分为四组：完整LP组(组1)，肌成纤维细胞网络间细胞外基质(ECM)增多(组2)，两层肌成纤维细胞吞噬增厚的ECM(组3)，LP另外缺乏内侧肌纤维母细胞层(组4)。所有的肌成纤维细胞和扩张的小管都是完全分化的，这可以从a-平滑肌肌动蛋白、肌球蛋白重链、Calponin 1以及松弛介导的cGMP依赖的蛋白激酶I和磷酸二酯酶5的表达来证明。从第1组到第4组，完整的生精和直径/Lp比值逐渐降低，提示Lp的改变反映了生精的质量。第4组肌成纤维细胞层厚度增加，无细胞增殖，但CD34(+)细胞、造血祖细胞和造血祖细胞(肺纤维化)靠近小管。结论：肌成纤维细胞去分化不是LP相关的生精障碍的原因。因此，肌成纤维细胞可能在一定程度上是新近发展起来的，在纤维性LP改变的发展过程中可能作为关键角色参与精子发生障碍，但不是通过收缩功能障碍。
Background: In the human testis, myofibroblasts are the main cellular components of the lamina propria (LP) of seminiferous tubules. Thickened ('fibrotic') LP and dilated tubules are found in a large number of infertile patients, and myofibroblast dedifferentiation has been described in elderly men. It is not known, however, whether dedifferentiation of myofibroblasts is responsible for disturbed spermatogenesis associated with LP alterations.Methods: The LP of testicular tissue from infertile men (n = 35) was investigated by new histological and morphometric approaches, RT-PCR after laser microdissection and western blotting.Results: Myofibroblasts were found in the LP of all seminiferous tubules. On the basis of LP morphology, each tubule could be assigned to one of the four groups, which showed increasing pathology: intact LP (Group 1), increased extracellular matrix (ECM) in-between the network of myofibroblasts (Group 2), two layers of myofibroblasts engulfing thickened ECM (Group 3) and LP additionally lacking an inner myofibroblast layer (Group 4). All myofibroblasts of all groups and of dilated tubules were fully differentiated, as could be shown by the expression of a-smooth muscle actin, myosin heavy chain, calponin 1 as well as relaxation-mediating cGMP-dependent protein kinase I and phosphodiesterase 5. Independently of the clinical background, the same patterns of thickened LP were detectable. There was a gradual decrease in intact spermatogenesis and in diameter/LP ratio from Groups 1 to 4, indicating that patterns of LP alterations reflect the quality of spermatogenesis. The thickness of myofibroblast layers increased towards Group 4 without cell proliferation, but CD34(+) cells, marking cells of haematopoetic lineage and progenitor cells (in lung fibrosis), were found in close proximity to tubules.Conclusions: Data indicate that dedifferentiation of myofibroblasts is not responsible for disturbed spermatogenesis associated with LP alterations. Thus, myofibroblasts, presumably newly developed in part, might contribute to disturbed spermatogenesis as key players during development of fibrotic LP alterations but not by contractile dysfunction.