Prss54基因通过调控顶体颗粒定位和细胞骨架组织影响精子形成的作用机制研究

Acrosome is a special organelle that plays a key role in fertilization. Although several genes have been reported to be involved in acrosome biogenesis, the molecular mechanisms governing acrosome biogenesis are still not fully clarified. Our previous study found that Prss54-null male mice exhibited sperm malformation, defects in sperm-zona penetration and male subfertility. It was further found that the acrosomal granule was eccentrically detached in the acrosomal vesicle associated with an impairment of the cytoskeleton organization after Prss54 disruption, leading to asymmetrical caudal descent of the acrosomal vesicle as well as abnormal nuclear shaping during late spermiogenesis. At present, there is no report on the study of Prss54 function. Thus we propose the following hypothesis: Prss54 plays an important role in mouse spermiogenesis by regulating acrosomal granule localization and cytoskeleton organization. The purpose of this study is to determine the expression and localization of Prss54 at different steps of spermiogenesis, explore the effects of Prss54 on the expression and distribution of key genes related to acrosome biogenesis, as well as identify and verify potential interaction proteins of Prss54, multilayered at molecular, cellular, tissue and animal levels. The expected results are helpful to reveal the molecular mechanisms by which Prss54 regulates acrosomal granule localization and cytoskeleton organization, providing theoretical guidance for the clinical diagnosis and treatment of male fertility disorders and the development of targeted reproductive regulatory drugs.

顶体是一个特殊的细胞器，在受精过程中起关键作用。尽管多个基因已被报道参与了顶体生物发生，但调控顶体生物发生的分子机制仍未明了。我们前期研究发现，Prss54剔除雄鼠精子畸形、穿透明带障碍、生育力低下。进一步研究发现，Prss54剔除后顶体颗粒偏心游离在顶体囊泡中，且细胞骨架组织紊乱，导致精子形成后期不对称的顶体囊泡向后延伸及核成型异常。目前未见关于Prss54功能研究的报道。据此我们提出假说：Prss54通过调控顶体颗粒定位和细胞骨架组织而在小鼠精子形成过程中发挥重要作用。本课题拟从分子、细胞、组织及动物水平多层次明确Prss54在精子形成不同阶段的表达和定位；探讨Prss54对顶体生物发生关键基因的表达和分布的调控；发现并验证Prss54的潜在相互作用蛋白。预期结果有助于揭示Prss54调控顶体颗粒定位和细胞骨架组织的分子机制，为雄性生育障碍的临床诊治和开发靶向生殖调节药物提供理论指导。