PROBLEM: The lymphatic vasculature controls leukocytes trafficking and limits 
the adaptive immune response. In previous models of preeclampsia (PE), defective 
immune function caused by disruption of lymphangiogenesis was shown to be 
involved in the disease pathophysiology. Especially, the dysfunction of 
regulatory T cells (Treg) at the maternal-fetal interface may be one of the 
causes of severe PE. In particular, activation of Tregs to obtain immune 
tolerance requires adequate antigen presentation through the lymphatic system. 
We hypothesized that impaired lymphangiogenesis and imbalanced Tregs at the 
maternal-fetal interface are associated with the pathophysiology of severe PE. 
However, the current research addressing this hypothesis is limited. Therefore, 
to compare differences in lymphangiogenesis in severe PE and normal conditions, 
we aimed to examine the location of lymphatics at the maternal-fetal interface 
and to investigate the association between lymphangiogenesis and Tregs in severe 
PE.
METHOD OF STUDY: We obtained entire uterus from normal pregnant mice. Placental 
and fetal membranes, including decidua, were obtained from 10 pregnant women 
with severe PE and 10 gestational age-matched controls. Immunohistochemistry for 
LYVE1 was used to localize the distribution of lymphatic vessels and CD4, CD25, 
and FOXP3 for Treg.
RESULTS: LYVE1-positive vessels were present in the uterine wall of mice. 
LYVE1-positive lymphatic vessels were localized on the human decidua. Tubular 
lymphatics were abundant in the control decidua, but significantly reduced in 
severe PE. Furthermore, lymphatic vessel density correlated with the number of 
decidual Tregs.
CONCLUSION: Abnormal decidual lymphangiogenesis is associated with reduced 
numbers of decidual Tregs in severe PE.