Requirement of gap junctional intercellular communication for human villous trophoblast differentiation.
During pregnancy, the villous trophoblast develops from the fusion of cytotrophoblastic cells (CT) into a syncytiotrophoblast (ST), supporting the main physiological functions of the human placenta. Connexin43 (Cx43) is demonstrated in situ and in vitro in the villous trophoblast between CT and between CT and ST. Moreover, the presence of a gap junctional intercellular communication (GJIC) during in vitro trophoblast differentiation was previously demonstrated. Because the exchange of molecules through gap junctions is considered to play a major role in the control of cell and tissue differentiation, we studied the effects of a gap junctional uncoupler, heptanol, on morphological and functional trophoblast differentiation and on GJIC measured by the fluorescence recovery after photobleaching method. We found that when the GJIC was interrupted, CT still aggregated but fused poorly. This morphological effect was associated with a significant decrease of trophoblastic-specific gene expression (beta human chorionic gonadotropin and human chorionic somatomammotropin). This blocking action was reversible as demonstrated by recovery of GJIC and trophoblast differentiation process after heptanol removal. Moreover, the inhibition of the trophoblast differentiation did not affect Cx43 transcript expression and Cx43 protein expression. These data suggest that the molecular exchanges through gap junctions preceding cellular fusion are essential for trophoblast differentiation generating the multifunctional syncytiotrophoblast.
Cronier
Laurent
L
Laboratoire de Biomembranes et Signalisation cellulaire, Université de Poitiers, 86022 Poitiers cedex, France.
Frendo
Jean-Louis
JL
Defamie
Norah
N
Pidoux
Guillaume
G
Bertin
Gladys
G
Guibourdenche
Jean
J
Pointis
Georges
G
Malassine
Andre
A
D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D002824:Chorionic Villi / Q000187:drug effects / Q000502:physiology*; D018031:Connexin 43 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D015726:Giant Cells / Q000502:physiology; D019850:Heptanol / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D011247:Pregnancy; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D014327:Trophoblasts / Q000187:drug effects / Q000502:physiology*
D006063:Chorionic Gonadotropin; D018031:Connexin 43; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D019850:Heptanol; C022616:thiazolyl blue