Expression of N-Acetylglucosaminyltransferase III Promotes Trophoblast Invasion and Migration in Early Human Placenta
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Expression of N-Acetylglucosaminyltransferase III Promotes Trophoblast Invasion and Migration in Early Human Placenta
Reproductive Sciences 1-10 ª The Author(s) 2018 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1933719118765967 journals.sagepub.com/home/rsx
Qinyin Deng, MD1, Xiru Liu, MD2, Zhongmei Yang, MD1, and Lan Xie, MD1
Abstract Introduction: Trophoblast migration and invasion at the maternal–fetal interface are crucial events for normal placentation and successful pregnancy. This progress is well controlled by many placenta-specific factors. Inadequate trophoblast invasion results in poor placenta plantation or even complications such as preeclampsia. It has been shown that N-acetylglucosaminyltransferase III (GnT-III) participates in tumor invasion and metastasis as a suppressor; however, the expression of GnT-III and its role in normal pregnancy is unclear. Our objective was to characterize GnT-III expression and function during placental development and identify the underlying mechanisms. Methods: The expression of GnT-III in human placental tissue from the first trimester was determined by immunohistochemistry. The HTR8/SVneo cell line was used to investigate the effects of GnT-III on proliferation, apoptosis, migration/invasion, matrix metalloproteinase (MMP) 2/9 activity, and the expression of the tissue inhibitor of metalloproteinase (TIMP) 1/2 using cell 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays, flow cytometric analysis, transwell migration/invasion assays, gelatin zymography, and Western blot, respectively. Moreover, a placental villous explant model was employed to determine its functions in placentation. Results: In the first-trimester placental tissue, GnT-III was localized within the cytotrophoblast, the syncytiotrophoblast and the trophoblast columns of human placental villi, decidual cells, and some extravillous cells in the maternal decidua. GnT-III silencing significantly inhibited HTR8/SVneo cell invasion and migration as well as extravillous explant outgrowth. The application of GnT-III siRNA significantly attenuated MMP2/9 activity and increased TIMP1/2 expression. Discussion and Conclusion: GnT-III is expressed in trophoblasts during normal human pregnancy and is involved in regulating trophoblast function. Keywords N-acetylglucosaminyltransferase III (GnT-III), placenta, trophoblast, invasion/migration
Introduction The placenta is a transient organ that forms during pregnancy and contributes to successful pregnancy.1,2 During human placental development, trophoblast invasion is very important. In the early stage of pregnancy, cytotrophoblast (CTBs) cells acquire an invasive phenotype and differentiate into extravillous trophoblasts (EVTs), which can invade the decidua and a portion of the myometrium or remodel the maternal vasculature. The syncytiotrophoblast (STB) is a terminally differentiated cell layer formed by the fusion of multiple CTBs. The STBs can cover the floating villi and mediate nutrient and gas exchange between
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