Characterization and Expression of Netrin-1 and Its Receptors UNC5B and DCC in Human Placenta

• Published in: The journal of histochemistry and cytochemistry 2010-01, Vol.58 (1), p.73-82
• Main Authors: Dakouane-Giudicelli, Mbarka, Duboucher, Christophe, Fortemps, Joanne, Missey-Kolb, Heliane, Brule, Daniele, Giudicelli, Yves, de Mazancourt, Philippe
• Format: Article
• Language: English
• Subjects: Abortion, Induced; Cell Adhesion; Cell Differentiation; Cell Division; Cell Movement; Cell Survival; DCC Receptor; DNA Primers; DNA, Complementary - genetics; Female; Gene Amplification; Humans; Immunohistochemistry; Nerve Growth Factors - genetics; Nerve Growth Factors - metabolism; Netrin-1; Placenta - cytology; Placenta - physiology; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Receptors, Cell Surface - genetics; Trophoblasts - cytology; Trophoblasts - physiology; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 0022-1554; 1551-5044
• DOI: 10.1369/jhc.2009.953463

Netrins are a family of proteins that mediate axonal guidance in the central nervous system (CNS). In addition to the CNS, netrins are involved in cell adhesion, motility, proliferation, differentiation, and survival. Because these processes occur in the placenta, we raised the question of whether netrin-1 is expressed by placental cells during development. In the present study, we analyzed the spatial and temporal distribution of netrin-1 and its two receptors, DCC (deleted in colorectal cancer) and UNC5B (uncoordinated-5 homolog) in human placenta using RT-PCR, Western blotting, and immunohistochemistry analysis. We demonstrated the presence of the proteins and transcripts of netrin-1 and its receptors in placenta and cytotrophoblasts. Furthermore, using immunohistochemistry, we localized endogenous netrin-1 protein staining to villous and extravillous cytotrophoblasts, and secreted netrin-1 outside the syncytiotrophoblasts. The DCC receptor was localized to syncytiotrophoblasts and invasive extravillous cytotrophoblasts during the first trimester and at term. On the other hand, the UNC5B receptor was localized to villous and extravillous cytotrophoblasts proximal to anchoring areas during the first trimester. At term, UNC5B was observed in decidual cells and weakly in extravillous cells. The discrete pattern of netrin-1 and netrin-1 receptor distribution suggested that netrin-1 protein functions might vary with its localization in the placenta and probably with time of gestation.