最近研究表明长链非编码RNA（lncRNA）参与调节人类生精细胞发育，但众多与精子发生相关的lncRNA及作用机制尚未明确。本课题组利用男性不育患者睾丸组织lncRNA表达芯片、小鼠生精细胞lncRNA分析以及生物信息学方法，筛选出精原细胞停滞型非梗阻性无精子症中具有潜在作用且相对保守的lncRNA Gm2044。初步研究发现Gm2044通过与其在染色体位置上相邻的干性基因Utf1 mRNA相互作用抑制后者翻译，并能调控精原细胞系的增殖。本课题组前期研究显示精原细胞停滞型非梗阻性无精子症睾丸组织中Gm2044和UTF1表达异常，但其具体作用及机制尚未阐明。本项目拟通过体内（人病理睾丸组织与基因修饰小鼠模型）和体外（睾丸精原细胞系）实验，研究Gm2044在精原细胞停滞型非梗阻性无精子症中的作用及其机制。探究lncRNA调控精子发生的分子信号通路，将为探讨男性不育发病原因和治疗提供新的线索。

Recent studies showed that long noncoding RNA (lncRNA) have been found to be involved in the regulation of human spermatogenic cell development. However, lncRNA associated with spermatogenesis and their mechanisms of action are unclear. Using lncRNA microarray of testicular tissue for male infertility, lncRNA analysis of mouse germ cells and bioinformatics methods, this project identify relatively conservative lncRNA Gm2044 which may play important roles in nonobstructive azoospermia of spermatogonial arrest. Preliminary studies demonstrated that Gm2044 can inhibit the adjacent chromosome location of stem gene Utf1 translation by interacting with Utf1 mRNA, and can also regulate the proliferation of spermatogonial cell line. Our previous studies showed that the Gm2044 and UTF1 protein are abnormally expressed in the testicular tissue for nonobstructive azoospermia of spermatogonial arrest, but the exact effect and mechanism have not been elucidated. This project intends to investigate the effect and mechanism of Gm2044 in nonobstructive azoospermia of spermatogonial arrest by using in vivio (human pathological tissue of testis and genetically modified mouse model) and in vitro (testicular spermatogonial cell lines) experiments. Understanding of the molecular signal pathway for lncRNA regulated spermatogenesis, will provide new clues to study pathogenesis and treat for patient with male infertility.