Molecular Human Reproduction, Vol. 8, No. 11, 1005-1013,
November 2002
© 2002 European Society of Human Reproduction and Embryology
Implantation and pregnancy |
Connexin expression and gap junctional intercellular communication in human first trimester trophoblast
1 LBSC, CNRS UMR 6558, Université de Poitiers, 86022 Poitiers cedex, 2 INSERM EMI 00-09, 06107 Nice Cedex 02, 3 LGPD/IBDM, 13288 Marseille cedex 9, 4 Departement d’Obstetriques et Gynecologie, CHR Citadelle, 4000 Liège, Belgium and 5 INSERM U427, Faculté de pharmacie, 4 Av. de l’observatoire, 75270 Paris cedex 6, France
Connexin (Cx) expression and gap junctional intercellular communication (GJIC) are involved in development and differentiation processes, and recently mutation of connexin genes has been implicated in pathologies. In the human placenta, two distinct differentiation pathways of cytotrophoblastic cells coexist and lead to a fusion phenotype (villous trophoblast) and a proliferative/invasive phenotype (extravillous trophoblast). Here we characterized in situ and in vitro the expression of Cx transcripts and proteins in the villous and extravillous trophoblast of first trimester placenta. In addition, the GJIC functionality was investigated using the gap–fluorescence recovery after photobleaching (gap-FRAP) method. We demonstrated in the villous trophoblast the presence of Cx43 mRNA and of Cx43 protein localized between cytotrophoblastic cells and between cytotrophoblastic cells and syncytiotrophoblast. In vitro, a transient functional gap junctional intertrophoblastic communication was demonstrated during the trophoblast fusion leading to the multinucleated syncytiotrophoblast. During the proliferative process of the extravillous trophoblast, Cx40 is expressed in the proximal part of the cell columns. When cytotrophoblastic cells were cultured on Matrigel® for 2 days, 
5ß1 integrin expression was observed concomitant with the presence of Cx40 mRNA and of Cx40 protein between the cells. No evidence for a GJIC was detected in this induced extravillous phenotype. In addition, Cx32 was detected between some aggregated cells after 72 h of culture. Our data show that the presence of Cx43 allows an inter-trophoblastic GJIC and is associated with the fusion process leading to the villous syncytiotrophoblast and that the presence of Cx40 does not allow GJIC and is associated with the extravillous phenotype.
connexin/extravillous trophoblast/gap junction/placenta/villous trophoblast
6 To whom correspondence should be addressed. E-mail: amalassi{at}pharmacie.univ-paris5.fr
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