Study of the Development and Function of the Uterine Lymphatics

摘要 淋巴系统是通过吸收和返回体内液体平衡的中心调节器 间质液回流到血液循环中;此外，它在脂质消化和免疫中起着关键作用， 炎症反应通过淋巴器官和免疫细胞运输。研究表明， 在子宫内存在子宫内膜异位症;然而，关于确切的发展和 子宫平滑肌的分布及其对子宫健康功能的影响。理解正确的 发育和维持神经系统可能具有临床重要性，因为神经系统已经 参与子宫内膜异位症等子宫疾病的发病机制和癌症转移。本研究 拟用Prox 1荧光淋巴管标记阐明子宫内膜异位症的发生和功能 报告基因和淋巴功能丧失小鼠模型。根据初步数据，我们假设 子宫动脉在产后子宫血管的引导下形成， 通过动情期的子宫重塑以维持子宫环境的流体动态平衡， 怀孕在描述了小鼠子宫平滑肌的正常发育后，我们将确定 在子宫组织液体引流和胚胎发育调节的背景下， 着床部位和妊娠。在整个发情期维持子宫内的液体平衡 和妊娠将通过实时示踪研究和湿/干组织重量比进行评估，而 将通过使用新的遗传学和外科手术方法， 可诱导的淋巴功能丧失小鼠模型。总之，这些研究成果将产生一个新的 了解小鼠子宫淋巴管的形态和功能，这可能提供一个有价值的新的 从这个角度来评估子宫健康。

Abstract The lymphatic system is the central regulator of fluid homeostasis in the body through absorbing and returning interstitial fluid back to blood circulation; additionally, it plays pivotal roles in lipid digestion and immune and inflammatory response through the lymphoid organs and immune cell trafficking. Studies have documented the presence of lymphatics in the uterus; however, little consensus exists regarding the exact development and distribution of the uterine lymphatics nor their impact on uterine health functions. Understanding the proper development and maintenance of the lymphatics may be of clinical importance, as lymphatics have been implicated in pathogenesis uterine diseases such as endometriosis and cancer metastasis. In this study, we propose to elucidate the development and functions of uterine lymphatics using Prox1 fluorescent lymphatic reporter and lymphatic loss of function mouse models. Based on preliminary data, we hypothesize that the uterine lymphatics develop postnatally under patterning guidance from uterine blood vessels, and that uterine lymphatics remodel to maintain fluid homeostasis of the uterine environment through estrous phases and pregnancy. After characterizing normal development of the murine uterine lymphatics, we will determine the function of uterine lymphatics in the context of fluid drainage of the uterine tissue and regulation of embryonic implantation sites and gestation. The maintenance of fluid homeostasis in the uterus through estrous phases and pregnancy will be assessed through real-time tracer studies and wet/dry tissue weight ratios, while the role of uterine lymphatics in embryonic implantation will be dissected through use of novel genetic and surgical inducible lymphatic loss of function mouse models. Together, these study outcomes will generate a novel understanding of murine uterine lymphatic morphology and function, which may provide a valuable new viewpoint from which to assess uterine health.