**4. Lymphangiogenesis**

Lymphatic vessels were first described in the 17th century and consists of a vascular-like network. They play a pivotal role in maintaining tissue fluid homeostasis, transport of proteins, macromolecules, and cells such as leucocytes and activated antigen-presenting cells for immune protection [52]. This vascular-like network consists of a monolayer of blind-ended capillaries transferring "lymph" to the collecting lymphatics. The expansion of new lymphatic vessels from pre-existing ones, called lymphangiogenesis, is controlled mainly by growth factors, i.e., VEGFs such as VEGF-C and its ligand VEGFR-3, VEGF-D [53–55], and other factors, i.e., hypoxia-inducible factor 1- α (HIF-1 α), the Tie/angiopoietin system, neuropilin-2, and integrinα9 [56–61]. However, until recently, there was a paucity of data on the lymphatic profile during pregnancy and in PE [62–64].

### *4.1. Lymphatic System in the Placenta*

The human placenta is an hemochorial organ and is highly vascularized; yet, there are conflicting reports on the presence of lymphatic vessels in the placenta. However, Gu et al. (2006) [65], Wang et al. (2011) [66], and Liu et al. (2015) [67], as well as our recent observations [68], do not confirm the presence of lymphatic vessels in the placenta. The aforementioned groups instead observed a stromal network immunostained with podoplanin. Lymphangiogenesis was observed at the decidua [68–72] and the uterine wall [64,73].
