Study of the Development and Function of the Uterine Lymphatics

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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.