title: Factors affecting cytotrophoblast cell viability and differentiation: Evidence of a link between syncytialisation and apoptosis.
abstract: A relationship between cytotrophoblast differentiation (syncytialisation) and apoptosis is hypothesised to exist, but has not been clearly determined. To address this, we explored the effects of cAMP, an inducer of syncytialisation, on human choriocarcinoma cell differentiation and viability under three different culture conditions related to diverse survival status: no serum, 10% fetal calf serum or 10% charcoal-stripped fetal calf serum. 8-Br-cAMP increased BeWo cell viability in culture media without serum, but viability was decreased in a dose- and time-dependent manner when serum was present. The appearance of apoptotic nuclei fragments were only observed when BeWo cells were cultured in media containing serum combined with 8-Br-cAMP treatment. In addition, the ratio of FasL to Fas expression following treatment with 8-Br-cAMP increased by 20-fold in 10% charcoal-stripped fetal calf serum media and 65-fold 10% fetal calf serum media, and activation of caspase-3 also required media with serum. The markers of syncytialisation (syncytin 1 expression and human chorionic gonadotropin secretion) were induced significantly by 8-Br-cAMP, and were higher in 10% fetal calf serum media than in 10% charcoal-stripped fetal calf serum media, than in the absence of serum. Syncytia formation was stimulated by 8-Br-cAMP and this required serum in the media. We now show that factors contained within serum are necessary for cAMP-stimulated cytotrophoblast differentiation, that syncytialisation involves apoptotic events, and that a lack of serum based factors could switch the cellular program away from differentiation.
authors.affiliation: Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Y X
authors.initials: YX
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Allars
authors.forename: K
authors.initials: K
authors.lastname: Maiti
authors.forename: G L
authors.initials: GL
authors.lastname: Angeli
authors.forename: C
authors.initials: C
authors.lastname: Abou-Seif
authors.forename: R
authors.initials: R
authors.lastname: Smith
authors.forename: R C
authors.initials: RC
authors.lastname: Nicholson
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002459:Cell Fusion; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005576:Colforsin / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D015726:Giant Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics
chemical_list: D015415:Biomarkers; D016895:Culture Media, Serum-Free; C491901:FAS protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate