申请人的前期研究发现猪子宫腔的闭合状态在胚胎附植前后显著变化，对胚胎附植成败有重要影响。子宫内膜细胞的集体迁移是宫腔闭合的重要细胞学基础，主导细胞集体迁移的E-钙黏素受到α2,6-唾液酸化修饰的调控，ST6GAL-1是催化该蛋白糖基化修饰形成的糖基转移酶，其表达模式与宫腔闭合变化相一致，暗示该基因介导的糖基化修饰在调控宫腔闭合状态中有重要功能。本项目将富集胚胎附植前后子宫内膜中差异表达的α2,6-唾液酸化糖蛋白并进行质谱鉴定，通过超表达和干扰实验验证ST6GAL-1基因对上述糖蛋白功能的调控作用，利用三维子宫内膜细胞培养技术鉴定影响细胞集体迁移的α2,6-唾液酸化糖蛋白及其信号通路，并在组织学水平和创制的抑制唾液酸化修饰的体内模型中进行验证，解析ST6GAL-1基因介导细胞集体迁移调控猪子宫腔闭合的机制，鉴定ST6GAL-1基因及其下游基因的功能突变，为猪产仔数的遗传改良提供新资料。

We observed that the endometrium migrates to the uterine lumen to cause the closure of the uterine lumen when embryo attaches to uterus. The structure can help to hold the embryo to the wall of the uterus to develop placenta and thus plays critical roles in implantation in pigs. The collective migration of endometrium is one cause for uterine closure. The E-cadherin which palys important role in uterine closure were regulated by α2,6-sialylation. ST6GAL-1, an glycosyltransferase that can induce α2,6-sialylation is expressed in endometrium and the pattern is consistent with the change of uterine closure. This implies that ST6GAL-1 gene may play important role in regulation of uterine closure through induction of α2,6-sialylation. In this project, The α2,6-sialylated protein expressed by endometrium during implantation will be enriched and characterized through LC-MS system. ST6GAL-1 gene will be overexpressed or knock-down to investigate its role in regulation of the function of the α2,6-sialylated protein. Three-dimensional cell culture will used to investigate the sialylated proteins and pathways that have impacts on collective migration of endometrium. In addition, we will use a developed successful technique for immobilizing osmotic pumps to deliver substances into the luminal cavity of the uterus in order to investigate the function of α2,6-sialylation on uterine closure in pigs. We will do genotyping for the identified mutation sites of key genes in pig population to investigate the association with litter size. The results will give insights to the mechanism involved in uterine closure that is mediated by ST6GAL-1 gene and provide useful markers for improvement of litter size in pigs.