Qinyin Deng1, Xiru Liu2, Zhongmei Yang1, Lan Xie1. 1. Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China. 2. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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.
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.
Entities:
Keywords:
N-acetylglucosaminyltransferase III (GnT-III); invasion/migration; placenta; trophoblast