title: Expression of PAPPA2 in human fetomaternal interface and involvement in trophoblast invasion and migration.
abstract: Pregnancy-associated plasma protein-A 2 (PAPPA2) is a placental-enriched gene that is important for normal human placentation and defects in the gene can cause complications in pregnancy. Yet the exact expression pattern and role of PAPPA2 in the human fetomaternal interface are not clear. In this study, in situ hybridization (ISH) and immunohistochemistry (IHC) were employed to examine the spatial and temporal expression of PAPPA2 in the human fetomaternal interface. IHC results exhibited wide expression of PAPPA2 in the fetomaternal interface, with placental syncytiatrophoblast (STB) and extravillous trophoblast (EVT) showing strong expression and the cytotrophoblast (CTB) showing weak expression of PAPPA2. These results were confirmed by ISH. Quantitative reverse transcription-polymerase chain reaction and western blot showed the elevation of PAPPA2 in first trimester EVT differentiation and term CTB spontaneous syncytialization. PAPPA2-siRNA transfection significantly depressed the invasion and migration ability of a trophoblast cell line (HTR8/SVneo) in a transwell migration and Matrigel invasion model compared to a negative control siRNA (P < 0.05), also revealing that matrix metalloproteinase 9 (MMP9) secretion is downregulated. This was confirmed using a human first trimester placental villi explant culture model. Our results reveal the spatial and temporal expression of PAPPA2 in the human fetomaternal interface and show the positive regulatory role of PAPPA2 in human trophoblast invasion and migration through the secretion of MMP9.
authors.affiliation: Beijing Shijitan Hospital, Capital Medical University, Beijing, China.|Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China.
authors.forename: H Y
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Anhui Medical University, Hefei, Anhui, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China songyu9649@163.com.
authors.forename: S
authors.initials: S
authors.lastname: Yu
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000201:enzymology / Q000502:physiology; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D010929:Placentation / Q000502:physiology; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014327:Trophoblasts / Q000201:enzymology* / Q000502:physiology
chemical_list: D012333:RNA, Messenger; C430889:PAPPA2 protein, human; D011266:Pregnancy-Associated Plasma Protein-A; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9