Expression of pregnancy-associated plasma protein-A (PAPP-A) during human villous trophoblast differentiation in vitro.
Pregnancy-associated placental protein-A (PAPP-A), first isolated from maternal serum, has been identified as a metalloprotease cleaving insulin-like growth factor binding protein-4 (IGFBP-4). The source of PAPP-A during pregnancy is unclear. We therefore investigated PAPP-A expression during in vitro human villous cytotrophoblast cell (CT) differentiation into syncytiotrophoblast (ST). CT were isolated from normal first trimester, second trimester and term placentae (n=10) and cultured to form ST. PAPP-A mRNA was quantified by real-time PCR, and PAPP-A protein expression was studied by immunocytochemistry and TRACE technology with specific monoclonal antibodies. PAPP-A mRNA expression in total placental extracts increased during the course of pregnancy. PAPP-A protein was detected in the cytoplasm of both CT and ST. ST formation in vitro was associated with a 19-fold increase in PAPP-A mRNA expression and an 8-fold increase in PAPP-A secretion into the culture medium. No significant difference in PAPP-A production was observed between cultured cells isolated from early and term placentae. In conclusion, PAPP-A production in vitro, is associated to the differentiation of villous cytotrophoblast cells into syncytiotrophoblast, independently of the age of gestation.
Unite INSERM U427, faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de I'observatoire, 75270 Paris, France.
J
J
Guibourdenche
J-L
JL
Frendo
G
G
Pidoux
G
G
Bertin
D
D
Luton
F
F
Muller
D
D
Porquet
D
D
Evain-Brion
D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007743:Labor, Obstetric; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
D017931:DNA Primers; D012333:RNA, Messenger; D011266:Pregnancy-Associated Plasma Protein-A