中科院学者Autophagy发现自噬导致畸形精子症新机制

　近期，中国科学院动物研究所李卫研究组发现自噬在支持细胞中参与外质特化结构的组装，支持细胞中自噬相关基因的缺失会导致畸形精子症的发生。该项研究成果在线发表在3月17日的autophagy 杂志上。

目前，全世界范围内人类精子数量下降、活力降低、畸形率增加，处于大规模城市化过程中的我国，不孕不育发病率已飙升至10-15%。男性不育病因非常复杂, 许多内外因素均可导致男性不育，其中精子畸形是重要原因之一。体细胞-生殖细胞互作是精子发生过程中几个至关重要的环节。支持细胞（Sertoli cell）除了形成血睾屏障构筑精子发生的微环境以外，还通过外质特化结构等与生殖细胞之间交互作用参与精子头部特定形态建成。但是外质特化结构组装的分子机制还不甚清楚，研究人员发现支持细胞中自噬流被阻断以后会导致大量畸形精子的产生。进一步的研究发现自噬在支持细胞中通过降解pDLIM1参与在外质特化结构的组装过程当中，而自噬相关基因在支持细胞中缺失以后会因为外质特化结构组装异常导致精子头部不能正确塑形，最终导致其育性严重下降。上述研究揭示了自噬通过调节细胞骨架组装参与支持细胞中外质特化结构组装的新机制，说明自噬与畸形精子症的发生密切相关。

动物所博士生刘超为该文第一作者。该研究课题受到国家自然基金（31171374，31471277）和发育与生殖重大研究计划（2012CB944404）项目的支持。

原文摘要：

Autophagy is required for ectoplasmic specialization assembly in Sertoli cells

The ectoplasmic specialization (ES) is essential for Sertoli-germ cell communication to support all phases of germ cell development and maturity. Its formation and remodeling requires rapid reorganization of the cytoskeleton. However, the molecular mechanism underlying the regulation of ES assembly is still largely unknown. Here, we show that Sertoli cell-specific disruption of autophagy influenced male mouse fertility due to the resulting disorganized seminiferous tubules and spermatozoa with malformed heads. In autophagy-deficient mouse testes, cytoskeleton structures were disordered and ES assembly was disrupted. The disorganization of the cytoskeleton structures might be caused by the accumulation of a negative cytoskeleton organization regulator, pDLIM1, and these defects could be partially rescued by pdlim1 knockdown in autophagy-deficient Sertoli cells. Altogether, our works reveal that the degradation of pDLIM1 by autophagy in Sertoli cells is important for the proper assembly of the ES, and these findings define a novel role for autophagy in Sertoli cell-germ cell communication.