睾丸源性miR-29c对精子DNA损伤调控的研究

精子DNA损伤是引起男性不育的常见原因，与流产和出生缺陷也有密切关系。研究证实miRNA在精子发生中不可或缺，并参与体细胞中DNA损伤修复的调控，因此我们推测miRNA可能是精子DNA损伤调控的重要因子。本课题组前期通过高通量测序筛选出在精浆中能稳定检测到的睾丸来源miRNAs，将其在精子DNA损伤严重的患者中筛选，再将筛选出差异性表达的miRNAs在动物实验中验证，发现miR-29c与精子DNA损伤相关。因此我们推断：miR-29c可能在睾丸中参与调控精子DNA损伤。为证实此推断并研究其作用机制，本项目拟开展miR-29c在人睾丸和精浆中表达的相关性研究，并检测miR-29c在睾丸中的定位和表达，鉴定其靶基因后进行信号通路研究和其下调的原因，来揭示miR-29c对精子DNA损伤的机制。此外本项目利用精浆的易获得性取代睾丸活检，从而为无创性方法研究睾丸内生理和病理过程提供重要手段。

Sperm DNA damage is an important factor that contribute to male infertility，and is also closely related to abortion and birth defects. It is confirmed that the miRNAs are indispensable in spermatogenesis, and participate in the regulation of cellular DNA damage and repair. Therefore, we speculated that miRNA might be a crucial part in the regulation process of sperm DNA damage. In our preliminary studies, we screened the testicular source miRNAs which were stably in the seminal plasma by high-throughput sequencing in patients with serious sperm DNA damage. The differentially expressed miRNAs were verified in mice and miR-29c was found to be associated with sperm DNA damage. Therefore, we hypothesize that miR-29c involves in the regulation process of sperm DNA damage in the testis. To confirm this hypothesis and explore its mechanism, we apply this project to study the localization and expression of miR-29c in testis in mice, the identification of target genes, and pathways and mechanism of regulation of miR-29c expression in sperm DNA damage. In addition, we use the seminal plasma, which is easy to access, to replace testicular biopsy in our research, which will provide an important means for noninvasive method to study the physiological and pathological processes in the testis.