Biological importance of podoplanin expression in chorionic villous stromal cells and its relationship to placental pathologies

Abstract

Podoplanin, a reliable marker of lymphatic endothelium, is a mucin-type transmembrane protein. Although the human placenta is devoid of a lymphatic system, chorionic villous stromal (CVS) cells express podoplanin. In this study, the pattern of podoplanin expression in normal and pathological placental tissues and the biological role of podoplanin were investigated. In total, 198 placental tissues belonging to 184 patients, seen at the Department of Pathology of Bulent Ecevit University Education and Research Hospital, Zonguldak, Turkey, were evaluated histopathologically and determined to meet the study criteria. The tissues were assigned to control, cisternal placental disorders, inflammation and hypoxic-ischemic pathology groups. Podoplanin expression in CVS cells was graded from 0 to 3 depending on the staining intensity, as determined by an immunohistochemical evaluation of chorionic villi in the most intensively stained tissue region. Podoplanin levels in control CVS cells increased in parallel with placental maturation, whereas in molar pregnancies podoplanin expression was lower than in control tissues. In the acute placental inflammation group, podoplanin immunoreactivity was similar to that in the control group, whereas in the preeclampsia group, podoplanin expression was higher than in all other groups. Our study showed an increase in podoplanin expression in CVS cells during pregnancy. In preeclamptic patients, the increase in podoplanin expression may be a response to hypoxic-ischemic conditions, whereas in molar pregnancies the decrease in podoplanin levels may cause villous swelling by disrupting intercellular fluid homeostasis.

Increased Angiogenesis and Lymphangiogenesis in the Placental Villi of Women with Chronic Venous Disease during Pregnancy

“…Podoplanin (D2-40) was also higher in these patients. Our results are consistent with the results of Kandemir et al [29], showing that podoplanin was increased in the placenta of women with vascular disorders. It should be noted that podoplanin, a mucin-like transmembrane protein, is a specific marker of lymphatic endothelium [30].…”

“…Podoplanin-expressing stromal cells can function as primitive lymphatic vessels [32]. Podoplanin plays a role in foetal angiogenesis during placental development, and abnormal activity leads to pregnancy diseases associated with defective angiogenesis [29,32,33]. Podoplanin expression in the human placenta has been suggested as a response to hypoxic-ischaemic conditions [29].…”

“…Podoplanin plays a role in foetal angiogenesis during placental development, and abnormal activity leads to pregnancy diseases associated with defective angiogenesis [29,32,33]. Podoplanin expression in the human placenta has been suggested as a response to hypoxic-ischaemic conditions [29]. Placental villi of women with CVD have shown increased expression of hypoxia markers, such as hypoxia-inducible factor-1α [10].…”

The origins of placental mesenchymal stromal cells: Full spectrum flow cytometry reveals mesenchymal heterogeneity in first trimester placentae, and phenotypic convergence in culture

“…Several studies have demonstrated that inhibiting CD26 enhances homing, engraftment and differentiation of hematopoietic stem cells (Christopherson et al ., 2004; Kawai et al ., 2007), and thus a lack of CD26 expression on CD73 + CD90 + cells could suggest they are involved in blood lineage migration/differentiation as both Hofbauer cells (placental macrophages) and nucleated red blood cells are found in the villous stroma in the first trimester (Van Handel et al ., 2007). Furthermore, podoplanin identifies connective stroma in lymphoid organs that produces a network of collagen-rich fibres to enable movement of lymphocytes via interactions with leukocyte CLEC-2 receptors (Link et al ., 2011; Nazari et al ., 2016; Onak Kandemir et al ., 2019; Wang et al ., 2011). The stroma of early placental villi is poorly vascularised therefore podoplanin + cells could enable blood lineage cells (including Hofbauer cells) to migrate throughout the villous core (Ingman et al ., 2010).…”

Epitope Analysis of an Anti-Whale Podoplanin Monoclonal Antibody, PMab-237, Using Flow Cytometry

“…(12) The expression of PDPN in chorionic villous stromal cells is in two important placental pathologies: preeclampsia and hydatidiform mole. (13) Moreover, PDPN is upregulated in many cancers and is involved in cancer metastasis and malignant progression. (14)(15)(16)(17) Recent reports showed that PDPN is related to a progression in oral epithelial dysplasia and oral squamous cell carcinoma through a co-expression with sex-determining region Y-related Homeo box gene 2.…”