Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Aulweg 123, 35385 Giessen, Germany.
Hum Reprod. 2011 Jun;26(6):1450-61. doi: 10.1093/humrep/der077. Epub 2011 Apr 5.
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.
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.
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 α-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.
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.
在人类睾丸中，肌成纤维细胞是生精小管固有层（LP）的主要细胞成分。在大量不育患者中发现 LP 增厚（“纤维化”）和小管扩张，并且在老年男性中已描述了肌成纤维细胞去分化。然而，尚不清楚肌成纤维细胞的去分化是否是与 LP 改变相关的精子发生障碍的原因。
通过新的组织学和形态计量学方法、激光微切割后的 RT-PCR 和 Western blot 分析，研究了不育男性睾丸组织的 LP。
在所有生精小管的 LP 中均发现了肌成纤维细胞。根据 LP 形态，每个小管都可以分配到四个组之一，这些组显示出逐渐增加的病理学：完整的 LP（第 1 组）、肌成纤维细胞网络之间的细胞外基质（ECM）增加（第 2 组）、两层肌成纤维细胞包裹增厚的 ECM（第 3 组）和 LP 另外缺乏内层肌成纤维细胞层（第 4 组）。所有组和扩张小管的所有肌成纤维细胞均为完全分化，这可以通过表达α-平滑肌肌动蛋白、肌球蛋白重链、钙调蛋白 1 以及松弛调节 cGMP 依赖性蛋白激酶 I 和磷酸二酯酶 5 来证明。独立于临床背景，均可检测到相同的 LP 增厚模式。从第 1 组到第 4 组，完整的精子发生和直径/ LP 比值逐渐降低，表明 LP 改变的模式反映了精子发生的质量。肌成纤维细胞层的厚度向第 4 组增加而没有细胞增殖，但在靠近小管的地方发现了 CD34（+）细胞，这些细胞标记着造血谱系和祖细胞（在肺纤维化中）。
数据表明，LP 改变相关的精子发生障碍与肌成纤维细胞的去分化无关。因此，肌成纤维细胞可能部分由新开发的细胞组成，可能作为纤维化 LP 改变发展过程中的关键参与者而不是通过收缩功能障碍来促进精子发生障碍。
