Structural and Functional Studies of the Uterine Lymphatics

PROGRAM SUMMARY The uterus is a highly-fluid dynamic organ that experiences significant structural and physiological changes throughout the estrus cycles, embryo implantation, pregnancy, and post-delivery. We aim to advance our understanding of the development, structure, and function of uterine lymphatics, focusing on their pivotal roles in fluid regulation and immune support during both pregnant and non-pregnant states. The project sets out to trace the postnatal development of lymphatics in mouse uterus, documenting significant physiological adaptations that occur during pregnancy. Of particular interest is the emergence of "lymphatic sphincters," unique structures we hypothesized to manage increased fluid volumes that are critical for fetal development and maternal health. By exploring how these lymphatics adapt and remodel during pregnancy, we aim to illuminate their crucial role in maintaining uterine health. Furthermore, the study will investigate how alterations in lymphatic function might affect the placement and spacing of embryo implantation sites, potentially impacting fetal-maternal interactions and influencing overall gestational outcomes. Through a variety of experimental approaches, including the surgical obstruction of lymphatic drainage, we will analyze changes in fluid dynamics and vascular remodeling across different reproductive states - from the various phases of the estrous cycle in non-pregnant conditions to dynamic shifts during pregnancy. By providing vital insights into the complex roles of uterine lymphatics in reproductive health, our research program seeks to fill significant gaps in our current understanding and pave the way for innovative treatments and strategies for managing pregnancy-related complications. The outcomes of our work could lead to groundbreaking advancements in gynecological and reproductive medicine, transforming approaches to enhancing fertility and managing reproductive health disorders. Through detailed study and innovative methodologies, our proposed study will help to establish a foundation for future clinical applications and therapeutic strategies, potentially transforming the landscape of women's health.