卵巢型子宫内膜异位症中异位灶来源干细胞对原位子宫内膜容受性的表观遗传学影响机制及CXCL12/CXCR4轴对其调控的探讨

Endometriosis is the growth of endometrial tissue outside the uterus and related with female infertility. Our previous studies have confirmed that stem cells are capable of circulating stem cells and migrate to the eutopic endometrium. Studies have shown that endometriosis-derived stem cells have similar phenotypes comparing with normal endometrial stem cells, but the former show significantly enhanced invasion, expansion and angiogenesis, suggesting potential epigenetic differences between them. We believe the migrations of endometriosis-derived endometrial stem cells to the eutopic endometrium may affect the latter's epigenetic patterns, resulting in receptivity-related gene expression disorders. It indicates an important epigenetic pathogenesis of endometriosis related pregnancy. We have previously found the regulation roles of CXCL12 / CXCR4 axis about ectopic endometrial mobilization into the circulation and migration to the target organs . Therefore, we seek to study the differences of Long Non-coding RNA expression patterns and endometrial receptivity in eutopic endometrium between endometriosis patients and control group. We plan to use NOD / SCID mouse endometriosis model to analyze the expression of Long Non-coding RNA and its effects on eutopic endometrial receptivity. In order to explore the blocking pathway of endometriosis-derived stem cells migrating to eutopic endometrium, the CXCL12 / CXCR4 axis will be adjusted.

子宫内膜异位症是常见疾病，与女性不孕相关。我们前期研究证实内异灶来源细胞表达干细胞相关因子，倾向性迁移到原位子宫内膜。研究表明异位灶来源干细胞与正常子宫内膜干细胞表型相似但行为学差异，提示两者具有表观遗传学差异。我们认为，子宫内膜异位灶来源干细胞向原位内膜迁移可能影响了后者的表观遗传学模式，导致容受性相关基因表达紊乱，成为子宫内膜异位症引起不孕的重要发病机制。我们还发现异位灶内膜的动员入血及迁移至靶器官受CXCL12/CXCR4轴的调控。因此，本研究的拟研究子宫内膜异位症患者及对照组原位子宫内膜Long Non-coding RNA表达模式及容受性差异，利用NOD/SCID小鼠子宫内膜异位症模型，异位灶来源细胞，解析异位灶来源细胞Long Non-coding RNA表达模式。并通过调控CXCL12/ CXCR4轴，探索异位灶来源细胞向原位内膜迁移的阻断途径。

子宫内膜异位症是子宫内膜组织在子宫外的生长的常见疾病，与女性不孕相关。我们前期研究证实内异灶来源细胞表达干细胞相关因子，能够通过血液循环，倾向性迁移到原位子宫内膜。有研究表明异位灶来源干细胞与正常子宫内膜干细胞有相似的表型，但前者表现出了显著增强的侵袭、扩增和血管形成能力，并提示两者具有潜在表观遗传学差异。我们认为，子宫内膜异位灶来源干细胞向原位内膜迁移后，可能影响了后者的表观遗传学模式，从而使容受性相关基因表达紊乱，成为子宫内膜异位症引起不孕的重要发病机制。我们之前研究发现异位灶内膜的动员入血及迁移至靶器官，均受CXCL12/CXCR4轴的调控。因此，本研究的拟研究子宫内膜异位症患者及对照组原位子宫内膜Long Non-coding RNA表达模式及容受性差异，利用NOD/SCID小鼠子宫内膜异位症模型，分选异位灶来源细胞，解析其Long Non-coding RNA表达模式及其对原位子宫内膜容受性干扰的机制。并利用SDF-1及AMD3100调节CXCL12/ CXCR4轴，探索异位灶来源细胞向原位内膜迁移的阻断途径。