Aberrant Expression of Dynein light chain 1 (DYNLT1) is Associated with Human Male Factor Infertility
Aberrant Expression of Dynein light chain 1 (DYNLT1) is Associated with Human Male Factor Infertility
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DOI：
10.1074/mcp.m115.050005
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发表时间：
2015-12-01
影响因子：
7
通讯作者：
Kumar, Pradeep G.
中科院分区：
文献类型：
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作者：
Indu, Sivankutty;Sekhar, Sreeja C.;Kumar, Pradeep G.
DYNLT1是在老鼠的t-复合体中发现的一个基因家族的成员，该基因与老鼠和苍蝇的雄性生殖细胞发育和功能有关。尽管在这两种模型中，该基因的表达缺陷都与男性不育有关，但还没有研究检查它与人类男性生精缺陷的关系。在这项研究中，我们评估了DYNLT1及其表达产物在有生育能力的男性和患有生精缺陷的男性生殖细胞中的水平。应用聚合酶链式反应和免疫印迹技术对正常生育男性(n=14)、弱精子症(n=15)、少精子症(n=20)和畸精症男性(n=23)进行了筛选。半定量聚合酶链式反应显示，与生育对照组相比，来自三个不育综合征组的几名患者的生殖细胞中DYNLT1的表达水平要么未检测到，要么显著降低。DYNLT1定位于正常生育男性精子的头部、中段和尾部。不育男性的精子出现DYNLT1的完全缺失或尾部缺失。大多数不育个体在精子上的DYNLT1定位水平可以忽略不计。DYNLT1在GC1-spg细胞中的过表达导致参与细胞周期调控的几种细胞骨架蛋白和分子伴侣的表达上调。在我们的研究人群中，DYNLT1的表达缺陷与男性因素不育综合征相关。过表达DYNLT1的GC1-spg细胞蛋白质组水平的变化提示其可能在生殖细胞发育中发挥作用。根据DYNLT1已知的功能，包括蛋白运输、膜泡形成、细胞周期调节和干细胞分化，我们讨论了这些观察的意义。
DYNLT1 is a member of a gene family identified within the t-complex of the mouse, which has been linked with male germ cell development and function in the mouse and the fly. Though defects in the expression of this gene are associated with male sterility in both these models, there has been no study examining its association with spermatogenic defects in human males. In this study, we evaluated the levels of DYNLT1 and its expression product in the germ cells of fertile human males and males suffering from spermatogenic defects. We screened fertile (n = 14), asthenozoospermic (n = 15), oligozoospermic (n = 20) and teratozoospermic (n = 23) males using PCR and Western blot analysis. Semiquantitative PCR indicated either undetectable or significantly lower levels of expression of DYNLT1 in the germ cells from several patients from across the three infertility syndrome groups, when compared with that of fertile controls. DYNLT1 was localized on head, mid-piece, and tail segments of spermatozoa from fertile males. Spermatozoa from infertile males presented either a total absence of DYNLT1 or its absence in the tail region. Majority of the infertile individuals showed negligible levels of localization of DYNLT1 on the spermatozoa. Overexpression of DYNLT1 in GC1-spg cell line resulted in the up-regulation of several cytoskeletal proteins and molecular chaperones involved in cell cycle regulation. Defective expression of DYNLT1 was associated with male factor infertility syndromes in our study population. Proteome level changes in GC1-spg cells overexpressing DYNLT1 were suggestive of its possible function in germ cell development. We have discussed the implications of these observations in the light of the known functions of DYNLT1, which included protein trafficking, membrane vesiculation, cell cycle regulation, and stem cell differentiation.