Monocultures of different placental cells are used for many physiological and toxicological studies; however, they are not a true reflection of the interaction between placenta and fetus. To develop the most appropriate model to study endocrine and metabolic properties of fetoplacental unit we used three co-culture models of placental cells nonfusogenic JEG-3, unsyncytialised BeWo (BeWo) and syncytialised BeWo (syncBeWo) cultured with adrenal (H295R) cells. As an end point of endocrine properties we investigated steroids receptors expression and steroid secretion, while as metabolic properties AhR, CYP1A1and COMT expression. Progesterone (P4), estradiol (E2) and human chorionic gonadotropin (hCG) secretion (ELISA) and 3βHSD, CYP19, estrogen (ERα/β), progesterone (PR) and aryl hydrocarbon (AhR) receptors, CYP1A1 and COMT protein expression (Western blot) were evaluated. Comparing three co-culture models we observed: (1) there were no differences between JEG-3 and BeWo in the PR expression, however it was higher in BeWo compared to syncBeWo; (2) there were no differences in ERα protein expression in all models, while profile of ERβ expression was the highest in syncBeWo; (3) high P4 secretion in JEG-3 and BeWo while low in syncBeWo; (4) high E2 levels in JEG-3 and syncBeWo, while low E2 secretion in BeWo; (5) the highest hCG secretion in the JEG-3 and syncBeWo than in BeWo (6) the highest AhR, CYP1A1 and COMT expression in syncBeWo. Based on the results showing higher hCG secretion in the JEG-3 than in BeWo, representing villous and extravillous phenotype we suggest that JEG-3 model could be used to study fetoplacental steroidogenesis at the 1st, while BeWo model at the 3rd. Results showing comparable profiles of AhR, CYP1A1 and COMT expression in JEG-3 and BeWo models and the significantly higher expression in synBeWo points to synBeWo as a good model for study the metabolic properties.