Lymphatic System and Dysfunctions in the Context of Male and Female

The lymphatic vascular system is pivotal for maintaining fluid homeostasis, immune cell trafficking, and fat absorption. Lymphatic endothelial cells originate from venous progenitors, driven by PROX1, VEGF-C, and VEGFR-3 signaling, forming a network to perform these functions. The mature lymphatic system comprises capillary and connecting vessels that transport lymph from the interstitial space to the venous circulatory system. Lymph nodes facilitate immune responses, highlighting the system’s integral role in health and diseases. Lymphatic dysfunction contributes to various diseases, including inflammation, cancer, cardiovascular diseases, and neurodegenerative disorders. Despite inherent differences in lymphatic function and structure in males and females, these disparities are often overlooked. Lymphedema arises from compromised lymphatic function, with primary lymphedema caused by congenital defects and secondary by trauma or infection. Diseases like systemic lupus erythematosus and dermatomyositis involve lymphatic dysfunction. Lymphatics also influence blood pressure regulation, cancer metastasis, and cardiovascular health, with notable sex differences impacting disease prognosis and treatment responses. Estrogen influences lymphatic functions through estrogen receptors, impacting gene expression and signaling pathways with sex-dependent effects. To summarize, this chapter will explore the notable sex-dependent differences specific to lymphatic biology and related diseases.