Placental Lymphatics In Pregnancy And Preeclampsia

Background: Preeclampsia is a disease of pregnancy that carries significant maternal morbidity and mortality worldwide with 16% of maternal deaths globally attributed to gestational hypertension. The pathogenesis of preeclampsia is thought to result from inadequate vascular remodeling during placentation with many research efforts focused on studying the anti-angiogenic and pro-inflammatory processes that occur in response to placental ischemia. Hypothesis: Given the known role of lymphatics in mediating inflammation, we hypothesize that insufficient lymphatic proliferation contributes to abnormal placentation and that augmenting lymphangiogenesis may reduce the severity of the disease. Methods: To test this hypothesis, we performed a systematic analysis of human placentas, as well as parietal and basal deciduas. Using immunohistochemistry we stained for lymphatic-specific markers including podoplanin, VEGFC and pan-endothelial marker CD31 and quantified their distribution and morphology. Results: Placentas revealed extensive podoplanin staining within the reticular networks of chorionic villous stromal cells. These same, podoplanin-positive villi, revealed the presence of VEGFC-positive structures. A similar staining pattern was observed in the basal deciduas, where podoplanin-positive decidual cells were found in close proximity to VEGFC-expressing cells. Parietal deciduas on the other hand revealed large lymphatic vessels in the vicinity of the fetal membranes. Conclusion: The abundance of lymphatic specific markers in the placenta and basal decidua hint at the potential existence of a lymphatic-like network within these structures but further functional analyses need to be conducted to understand their role. The dilated lymphatics found in the parietal decidua represent a concrete opportunity to compare lymphatic vessels between preeclamptic and healthy parietal deciduas. An overall better understanding of lymphatics in these tissues may offer new therapeutic strategies for a disease that is in desperate need for adequate treatment options.